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Special Issue "Lipopolysaccharides (LPSs)"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (30 September 2017)

Special Issue Editor

Guest Editor
Prof. Dr. Juan M. Tomás

Departamento de Genética, Microbiología y Estadística, Universidad de Barcelona, Diagonal 645, Barcelona 08071, Spain
Website | E-Mail
Interests: genomics and proteomics; chemical structure; host interaction; health applications

Special Issue Information

Dear Colleagues,

In Gram-negative bacteria, three layers surround the cytoplasm: An inner membrane, a layer of peptidoglycan, and an outer membrane. The outer membrane is an asymmetric lipidic bilayer, with phospholipids on its inner surface, and lipopolysaccharides (LPSs) on the outside, this being the major component of the outer leaflet, covering approximately nearly three quarters of the total outer cell surface.
All LPSs possess the same general chemical architecture, independently of the bacterial activity (pathogenic, symbiotic, commensal), ecological niches (human, animal, soil, plant, water), or growth conditions. Endotoxins are large amphiphilic molecules consisting of a hydrophilic polysaccharide part, and a covalently bound hydrophobic and highly conserved lipid component, termed lipid A (the endotoxin subunit). The polysaccharide part can be divided into two sub-domains: The internal and conserved, the core region, and one more external and highly variable, the O-specific chain, also named O-antigen for its immunogenic properties. LPSs are endotoxins, one of the most potent classes of activators of the mammalian immune system; they can be released from cell surfaces of bacteria during their multiplication, lysis, and death. LPS can acts through its biological center (lipid A component) on various cell types, of which macrophages and monocytes are the most important.

Prof. Dr. Juan M. Tomás
Guest Editor

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Keywords

  • biosynthesis
  • assembly
  • chemical structure
  • biological significance
  • genetics
  • modifications
  • immunity
  • vaccines

Published Papers (16 papers)

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Research

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Open AccessArticle The New Structure of Core Oligosaccharide Presented by Proteus penneri 40A and 41 Lipopolysaccharides
Int. J. Mol. Sci. 2018, 19(3), 676; https://doi.org/10.3390/ijms19030676
Received: 29 January 2018 / Revised: 16 February 2018 / Accepted: 22 February 2018 / Published: 28 February 2018
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Abstract
The new type of core oligosaccharide in Proteus penneri 40A and 41 lipopolysaccharides has been investigated by 1H and 13C NMR spectroscopy, electrospray ionization mass spectrometry and chemical methods. Core oligosaccharides of both strains were chosen for structural analysis based on
[...] Read more.
The new type of core oligosaccharide in Proteus penneri 40A and 41 lipopolysaccharides has been investigated by 1H and 13C NMR spectroscopy, electrospray ionization mass spectrometry and chemical methods. Core oligosaccharides of both strains were chosen for structural analysis based on the reactivity of LPSs with serum against P. penneri 40A core oligosaccharide–diphtheria toxoid conjugate. Structural analyses revealed that P. penneri 40A and 41 LPSs possess an identical core oligosaccharide. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle Biophysical Analysis of Lipopolysaccharide Formulations for an Understanding of the Low Endotoxin Recovery (LER) Phenomenon
Int. J. Mol. Sci. 2017, 18(12), 2737; https://doi.org/10.3390/ijms18122737
Received: 29 November 2017 / Revised: 11 December 2017 / Accepted: 13 December 2017 / Published: 16 December 2017
Cited by 2 | PDF Full-text (2807 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lipopolysaccharides (LPS, endotoxin) are complex and indispensable components of the outer membrane of most Gram-negative bacteria. They represent stimuli for many biological effects with pathophysiological character. Recombinant therapeutic proteins that are manufactured using biotechnological processes are prone to LPS contaminations due to their
[...] Read more.
Lipopolysaccharides (LPS, endotoxin) are complex and indispensable components of the outer membrane of most Gram-negative bacteria. They represent stimuli for many biological effects with pathophysiological character. Recombinant therapeutic proteins that are manufactured using biotechnological processes are prone to LPS contaminations due to their ubiquitous occurrence. The maximum endotoxin load of recombinant therapeutic proteins must be below the pyrogenic threshold. Certain matrices that are commonly used for recombinant therapeutic proteins show a phenomenon called “Low Endotoxin Recovery (LER)”. LER is defined as the loss of detectable endotoxin activity over time using compendial Limulus amebocyte lysate (LAL) assays when undiluted products are spiked with known amount of endotoxin standards. Because LER poses potential risks that endotoxin contaminations in products may be underestimated or undetected by the LAL assay, the United States (U.S.) Food and Drug Administration’s (FDA’s) Center for Drug Evaluation and Research (CDER) has recently started requesting that companies conduct endotoxin spike/hold recovery studies to determine whether a given biological product causes LER. Here, we have performed an analysis of different LPS preparations with relevant detergents studying their acyl chain phase transition, their aggregate structures, their size distributions, and binding affinity with a particular anti-endotoxin peptide, and correlating it with the respective data in the macrophage activation test. In this way, we have worked out biophysical parameters that are important for an understanding of LER. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle Structural Masquerade of Plesiomonas shigelloides Strain CNCTC 78/89 O-Antigen—High-Resolution Magic Angle Spinning NMR Reveals the Modified d-galactan I of Klebsiella pneumoniae
Int. J. Mol. Sci. 2017, 18(12), 2572; https://doi.org/10.3390/ijms18122572
Received: 8 November 2017 / Revised: 23 November 2017 / Accepted: 25 November 2017 / Published: 29 November 2017
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Abstract
The high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS NMR) analysis of Plesiomonas shigelloides 78/89 lipopolysaccharide directly on bacteria revealed the characteristic structural features of the O-acetylated polysaccharide in the NMR spectra. The O-antigen profiles were unique, yet the pattern
[...] Read more.
The high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS NMR) analysis of Plesiomonas shigelloides 78/89 lipopolysaccharide directly on bacteria revealed the characteristic structural features of the O-acetylated polysaccharide in the NMR spectra. The O-antigen profiles were unique, yet the pattern of signals in the, spectra along with their 1H,13C chemical shift values, resembled these of d-galactan I of Klebsiella pneumoniae. The isolated O-specific polysaccharide (O-PS) of P. shigelloides strain CNCTC 78/89 was investigated by 1H and 13C NMR spectroscopy, mass spectrometry and chemical methods. The analyses demonstrated that the P. shigelloides 78/89 O-PS is composed of →3)-α-d-Galp-(1→3)-β-d-Galf2OAc-(1→ disaccharide repeating units. The O-acetylation was incomplete and resulted in a microheterogeneity of the O-antigen. This O-acetylation generates additional antigenic determinants within the O-antigen, forms a new chemotype, and contributes to the epitopes recognized by the O-serotype specific antibodies. The serological cross-reactivities further confirmed the inter-specific structural similarity of these O-antigens. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle Time Response of Oxidative/Nitrosative Stress and Inflammation in LPS-Induced Endotoxaemia—A Comparative Study of Mice and Rats
Int. J. Mol. Sci. 2017, 18(10), 2176; https://doi.org/10.3390/ijms18102176
Received: 6 September 2017 / Revised: 1 October 2017 / Accepted: 9 October 2017 / Published: 18 October 2017
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Abstract
Sepsis is a severe and multifactorial disease with a high mortality rate. It represents a strong inflammatory response to an infection and is associated with vascular inflammation and oxidative/nitrosative stress. Here, we studied the underlying time responses in the widely used lipopolysaccharide (LPS)-induced
[...] Read more.
Sepsis is a severe and multifactorial disease with a high mortality rate. It represents a strong inflammatory response to an infection and is associated with vascular inflammation and oxidative/nitrosative stress. Here, we studied the underlying time responses in the widely used lipopolysaccharide (LPS)-induced endotoxaemia model in mice and rats. LPS (10 mg/kg; from Salmonella Typhosa) was intraperitoneally injected into mice and rats. Animals of every species were divided into five groups and sacrificed at specific points in time (0, 3, 6, 9, 12 h). White blood cells (WBC) decreased significantly in both species after 3 h and partially recovered with time, whereas platelet decrease did not recover. Oxidative burst and iNOS-derived nitrosyl-iron hemoglobin (HbNO) increased with time (maxima at 9 or 12 h). Immune cell infiltration (CD68 and F4/80 content) showed an increase with time, which was supported by increased vascular mRNA expression of VCAM-1, P-selectin, IL-6 and TNF-α. We characterized the time responses of vascular inflammation and oxidative/nitrosative stress in LPS-induced endotoxaemic mice and rats. The results of this study will help to interpret and compare data from different animal species in LPS-induced endotoxaemia models for the identification of new drug targets. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle Salmonella O48 Serum Resistance is Connected with the Elongation of the Lipopolysaccharide O-Antigen Containing Sialic Acid
Int. J. Mol. Sci. 2017, 18(10), 2022; https://doi.org/10.3390/ijms18102022
Received: 7 August 2017 / Revised: 9 September 2017 / Accepted: 12 September 2017 / Published: 21 September 2017
Cited by 1 | PDF Full-text (1265 KB) | HTML Full-text | XML Full-text
Abstract
Complement is one of the most important parts of the innate immune system. Some bacteria can gain resistance against the bactericidal action of complement by decorating their outer cell surface with lipopolysaccharides (LPSs) containing a very long O-antigen or with specific outer membrane
[...] Read more.
Complement is one of the most important parts of the innate immune system. Some bacteria can gain resistance against the bactericidal action of complement by decorating their outer cell surface with lipopolysaccharides (LPSs) containing a very long O-antigen or with specific outer membrane proteins. Additionally, the presence of sialic acid in the LPS molecules can provide a level of protection for bacteria, likening them to human cells, a phenomenon known as molecular mimicry. Salmonella O48, which contains sialic acid in the O-antigen, is the major cause of reptile-associated salmonellosis, a worldwide public health problem. In this study, we tested the effect of prolonged exposure to human serum on strains from Salmonella serogroup O48, specifically on the O-antigen length. After multiple passages in serum, three out of four tested strains became resistant to serum action. The gas-liquid chromatography/tandem mass spectrometry analysis showed that, for most of the strains, the average length of the LPS O-antigen increased. Thus, we have discovered a link between the resistance of bacterial cells to serum and the elongation of the LPS O-antigen. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle LPS-Induced Low-Grade Inflammation Increases Hypothalamic JNK Expression and Causes Central Insulin Resistance Irrespective of Body Weight Changes
Int. J. Mol. Sci. 2017, 18(7), 1431; https://doi.org/10.3390/ijms18071431
Received: 26 April 2017 / Revised: 22 June 2017 / Accepted: 27 June 2017 / Published: 4 July 2017
Cited by 4 | PDF Full-text (3035 KB) | HTML Full-text | XML Full-text
Abstract
Metabolic endotoxemia contributes to low-grade inflammation in obesity, which causes insulin resistance due to the activation of intracellular proinflammatory pathways, such as the c-Jun N-terminal Kinase (JNK) cascade in the hypothalamus and other tissues. However, it remains unclear whether the proinflammatory process precedes
[...] Read more.
Metabolic endotoxemia contributes to low-grade inflammation in obesity, which causes insulin resistance due to the activation of intracellular proinflammatory pathways, such as the c-Jun N-terminal Kinase (JNK) cascade in the hypothalamus and other tissues. However, it remains unclear whether the proinflammatory process precedes insulin resistance or it appears because of the development of obesity. Hypothalamic low-grade inflammation was induced by prolonged lipopolysaccharide (LPS) exposure to investigate if central insulin resistance is induced by an inflammatory stimulus regardless of obesity. Male Wistar rats were treated with single (1 LPS) or repeated injections (6 LPS) of LPS (100 μg/kg, IP) to evaluate the phosphorylation of the insulin receptor substrate-1 (IRS1), Protein kinase B (AKT), and JNK in the hypothalamus. Single LPS increased the expression of pIRS1, pAKT, and pJNK, whereas the repeated LPS treatment failed to recruit pIRS1 and pAKT. The 6 LPS treated rats showed increased total JNK and pJNK. The 6 LPS rats became unresponsive to the hypophagic effect induced by central insulin administration (12 μM/5 μL, ICV). Prolonged exposure to LPS (24 h) impaired the insulin-induced AKT phosphorylation and the translocation of the transcription factor forkhead box protein O1 (FoxO1) from the nucleus to the cytoplasm of the cultured hypothalamic GT1-7 cells. Central administration of the JNK inhibitor (20 μM/5 μL, ICV) restored the ability of insulin to phosphorylate IRS1 and AKT in 6 LPS rats. The present data suggest that an increased JNK activity in the hypothalamus underlies the development of insulin resistance during prolonged exposure to endotoxins. Our study reveals that weight gain is not mandatory for the development of hypothalamic insulin resistance and the blockade of proinflammatory pathways could be useful for restoring the insulin signaling during prolonged low-grade inflammation as seen in obesity. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle The Complete Structure of the Core Oligosaccharide from Edwardsiella tarda EIB 202 Lipopolysaccharide
Int. J. Mol. Sci. 2017, 18(6), 1163; https://doi.org/10.3390/ijms18061163
Received: 18 February 2017 / Revised: 10 April 2017 / Accepted: 24 May 2017 / Published: 31 May 2017
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Abstract
The chemical structure and genomics of the lipopolysaccharide (LPS) core oligosaccharide of pathogenic Edwardsiella tarda strain EIB 202 were studied for the first time. The complete gene assignment for all LPS core biosynthesis gene functions was acquired. The complete structure of core oligosaccharide
[...] Read more.
The chemical structure and genomics of the lipopolysaccharide (LPS) core oligosaccharide of pathogenic Edwardsiella tarda strain EIB 202 were studied for the first time. The complete gene assignment for all LPS core biosynthesis gene functions was acquired. The complete structure of core oligosaccharide was investigated by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry MSn, and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry. The following structure of the undecasaccharide was established: The heterogeneous appearance of the core oligosaccharide structure was due to the partial lack of β-d-Galp and the replacement of α-d-GlcpNAcGly by α-d-GlcpNGly. The glycine location was identified by mass spectrometry. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle Bordetella holmesii: Lipid A Structures and Corresponding Genomic Sequences Comparison in Three Clinical Isolates and the Reference Strain ATCC 51541
Int. J. Mol. Sci. 2017, 18(5), 1080; https://doi.org/10.3390/ijms18051080
Received: 10 March 2017 / Revised: 5 May 2017 / Accepted: 11 May 2017 / Published: 18 May 2017
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Abstract
Bordetella holmesii can cause invasive infections but can also be isolated from the respiratory tract of patients with whooping-cough like symptoms. For the first time, we describe the lipid A structure of B. holmesii reference strain ATCC 51541 (alias NCTC12912 or CIP104394) and
[...] Read more.
Bordetella holmesii can cause invasive infections but can also be isolated from the respiratory tract of patients with whooping-cough like symptoms. For the first time, we describe the lipid A structure of B. holmesii reference strain ATCC 51541 (alias NCTC12912 or CIP104394) and those of three French B. holmesii clinical isolates originating from blood (Bho1) or from respiratory samples (FR4020 and FR4101). They were investigated using chemical analyses, gas chromatography–mass spectrometry (GC–MS), and matrix-assisted laser desorption ionization–mass spectrometry (MALDI–MS). The analyses revealed a common bisphosphorylated β-(1→6)-linked d-glucosamine disaccharide with hydroxytetradecanoic acid in amide linkages. Similar to B. avium, B. hinzii and B. trematum lipids A, the hydroxytetradecanoic acid at the C-2′ position are carrying in secondary linkage a 2-hydroxytetradecanoic acid residue resulting of post-traductional biosynthesis modifications. The three clinical isolates displayed characteristic structural traits compared to the ATCC 51541 reference strain: the lipid A phosphate groups are more or less modified with glucosamine in the isolates and reference strain, but the presence of 10:0(3-OH) is only observed in the isolates. This trait was only described in B. pertussis and B. parapertussis strains, as well as in B. petrii isolates by the past. The genetic bases for most of the key structural elements of lipid A were analyzed and supported the structural data. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle Structural Characterization of Core Region in Erwinia amylovora Lipopolysaccharide
Int. J. Mol. Sci. 2017, 18(3), 559; https://doi.org/10.3390/ijms18030559
Received: 2 February 2017 / Revised: 24 February 2017 / Accepted: 28 February 2017 / Published: 4 March 2017
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Abstract
Erwinia amylovora (E. amylovora) is the first bacterial plant pathogen described and demonstrated to cause fire blight, a devastating plant disease affecting a wide range of species including a wide variety of Rosaceae. In this study, we reported the lipopolysaccharide
[...] Read more.
Erwinia amylovora (E. amylovora) is the first bacterial plant pathogen described and demonstrated to cause fire blight, a devastating plant disease affecting a wide range of species including a wide variety of Rosaceae. In this study, we reported the lipopolysaccharide (LPS) core structure from E. amylovora strain CFBP1430, the first one for an E. amylovora highly pathogenic strain. The chemical characterization was performed on the mutants waaL (lacking only the O-antigen LPS with a complete LPS-core), wabH and wabG (outer-LPS core mutants). The LPSs were isolated from dry cells and analyzed by means of chemical and spectroscopic methods. In particular, they were subjected to a mild acid hydrolysis and/or a hydrazinolysis and investigated in detail by one and two dimensional Nuclear Magnetic Resonance (NMR) spectroscopy and ElectroSpray Ionization Fourier Transform-Ion Cyclotron Resonance (ESI FT-ICR) mass spectrometry. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle Comparative Genomics of the Aeromonadaceae Core Oligosaccharide Biosynthetic Regions
Int. J. Mol. Sci. 2017, 18(3), 519; https://doi.org/10.3390/ijms18030519
Received: 7 February 2017 / Revised: 23 February 2017 / Accepted: 26 February 2017 / Published: 28 February 2017
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Abstract
Lipopolysaccharides (LPSs) are an integral part of the Gram-negative outer membrane, playing important organizational and structural roles and taking part in the bacterial infection process. In Aeromonas hydrophila, piscicola, and salmonicida, three different genomic regions taking part in the LPS
[...] Read more.
Lipopolysaccharides (LPSs) are an integral part of the Gram-negative outer membrane, playing important organizational and structural roles and taking part in the bacterial infection process. In Aeromonas hydrophila, piscicola, and salmonicida, three different genomic regions taking part in the LPS core oligosaccharide (Core-OS) assembly have been identified, although the characterization of these clusters in most aeromonad species is still lacking. Here, we analyse the conservation of these LPS biosynthesis gene clusters in the all the 170 currently public Aeromonas genomes, including 30 different species, and characterise the structure of a putative common inner Core-OS in the Aeromonadaceae family. We describe three new genomic organizations for the inner Core-OS genomic regions, which were more evolutionary conserved than the outer Core-OS regions, which presented remarkable variability. We report how the degree of conservation of the genes from the inner and outer Core-OS may be indicative of the taxonomic relationship between Aeromonas species. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle Identification and Characterization of Lipopolysaccharide Induced TNFα Factor from Blunt Snout Bream, Megalobrama amblycephala
Int. J. Mol. Sci. 2017, 18(2), 233; https://doi.org/10.3390/ijms18020233
Received: 19 October 2016 / Revised: 17 January 2017 / Accepted: 18 January 2017 / Published: 15 February 2017
Cited by 1 | PDF Full-text (1855 KB) | HTML Full-text | XML Full-text
Abstract
Lipopolysaccharide induced TNFα factor (LITAF) is an important transcription factor responsible for regulation of tumor necrosis factor α. In this study, a novel litaf gene (designated as Malitaf) was identified and characterized from blunt snout bream, Megalobrama amblycephala. The full-length cDNA of
[...] Read more.
Lipopolysaccharide induced TNFα factor (LITAF) is an important transcription factor responsible for regulation of tumor necrosis factor α. In this study, a novel litaf gene (designated as Malitaf) was identified and characterized from blunt snout bream, Megalobrama amblycephala. The full-length cDNA of Malitaf was of 956 bp, encoding a polypeptide of 161 amino acids with high similarity to other known LITAFs. A phylogenetic tree also showed that Malitaf significantly clustered with those of other teleost, indicating that Malitaf was a new member of fish LITAF family. The putative maLITAF protein possessed a highly conserved LITAF domain with two CXXC motifs. The mRNA transcripts of Malitaf were detected in all examined tissues of healthy M. amblycephala, including kidney, head kidney, muscle, liver, spleen, gill, and heart, and with the highest expression in immune organs: spleen and head kidney. The expression level of Malitaf in spleen was rapidly up-regulated and peaked (1.29-fold, p < 0.05) at 2 h after lipopolysaccharide (LPS) stimulation. Followed the stimulation of Malitaf, Matnfα transcriptional level was also transiently induced to a high level (51.74-fold, p < 0.001) at 4 h after LPS stimulation. Taken together, we have identified a putative fish LITAF ortholog, which was a constitutive and inducible immune response gene involved in M. amblycephala innate immunity during the course of a pathogenic infection. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessArticle Aspirin down Regulates Hepcidin by Inhibiting NF-κB and IL6/JAK2/STAT3 Pathways in BV-2 Microglial Cells Treated with Lipopolysaccharide
Int. J. Mol. Sci. 2016, 17(12), 1921; https://doi.org/10.3390/ijms17121921
Received: 30 September 2016 / Revised: 26 October 2016 / Accepted: 9 November 2016 / Published: 16 December 2016
Cited by 4 | PDF Full-text (1455 KB) | HTML Full-text | XML Full-text
Abstract
Aspirin down regulates transferrin receptor 1 (TfR1) and up regulates ferroportin 1 (Fpn1) and ferritin expression in BV-2 microglial cells treated without lipopolysaccharides (LPS), as well as down regulates hepcidin and interleukin 6 (IL-6) in cells treated with LPS. However, the relevant mechanisms
[...] Read more.
Aspirin down regulates transferrin receptor 1 (TfR1) and up regulates ferroportin 1 (Fpn1) and ferritin expression in BV-2 microglial cells treated without lipopolysaccharides (LPS), as well as down regulates hepcidin and interleukin 6 (IL-6) in cells treated with LPS. However, the relevant mechanisms are unknown. Here, we investigate the effects of aspirin on expression of hepcidin and iron regulatory protein 1 (IRP1), phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and P65 (nuclear factor-κB), and the production of nitric oxide (NO) in BV-2 microglial cells treated with and without LPS. We demonstrated that aspirin inhibited hepcidin mRNA as well as NO production in cells treated with LPS, but not in cells without LPS, suppresses IL-6, JAK2, STAT3, and P65 (nuclear factor-κB) phosphorylation and has no effect on IRP1 in cells treated with or without LPS. These findings provide evidence that aspirin down regulates hepcidin by inhibiting IL6/JAK2/STAT3 and P65 (nuclear factor-κB) pathways in the cells under inflammatory conditions, and imply that an aspirin-induced reduction in TfR1 and an increase in ferritin are not associated with IRP1 and NO. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Review

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Open AccessReview Coxiella burnetii Lipopolysaccharide: What Do We Know?
Int. J. Mol. Sci. 2017, 18(12), 2509; https://doi.org/10.3390/ijms18122509
Received: 29 September 2017 / Revised: 20 November 2017 / Accepted: 21 November 2017 / Published: 23 November 2017
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Abstract
A small gram-negative bacterium, Coxiella burnetii (C. burnetii), is responsible for a zoonosis called Q fever. C. burnetii is an intracellular bacterium that can survive inside microbicidal cells like monocytes and macrophages by hijacking several functions of the immune system. Among
[...] Read more.
A small gram-negative bacterium, Coxiella burnetii (C. burnetii), is responsible for a zoonosis called Q fever. C. burnetii is an intracellular bacterium that can survive inside microbicidal cells like monocytes and macrophages by hijacking several functions of the immune system. Among several virulence factors, the lipopolysaccharide (LPS) of C. burnetii is one of the major factors involved in this immune hijacking because of its atypical composition and structure. Thus, the aim of this mini-review is to summarize the repressive effects of C. burnetii LPS on the antibacterial immunity of cells. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
Open AccessReview The Glycosyltransferases of LPS Core: A Review of Four Heptosyltransferase Enzymes in Context
Int. J. Mol. Sci. 2017, 18(11), 2256; https://doi.org/10.3390/ijms18112256
Received: 29 September 2017 / Revised: 23 October 2017 / Accepted: 24 October 2017 / Published: 27 October 2017
PDF Full-text (9505 KB) | HTML Full-text | XML Full-text
Abstract
Bacterial antibiotic resistance is a rapidly expanding problem in the world today. Functionalization of the outer membrane of Gram-negative bacteria provides protection from extracellular antimicrobials, and serves as an innate resistance mechanism. Lipopolysaccharides (LPS) are a major cell-surface component of Gram-negative bacteria that
[...] Read more.
Bacterial antibiotic resistance is a rapidly expanding problem in the world today. Functionalization of the outer membrane of Gram-negative bacteria provides protection from extracellular antimicrobials, and serves as an innate resistance mechanism. Lipopolysaccharides (LPS) are a major cell-surface component of Gram-negative bacteria that contribute to protecting the bacterium from extracellular threats. LPS is biosynthesized by the sequential addition of sugar moieties by a number of glycosyltransferases (GTs). Heptosyltransferases catalyze the addition of multiple heptose sugars to form the core region of LPS; there are at most four heptosyltransferases found in all Gram-negative bacteria. The most studied of the four is HepI. Cells deficient in HepI display a truncated LPS on their cell surface, causing them to be more susceptible to hydrophobic antibiotics. HepI–IV are all structurally similar members of the GT-B structural family, a class of enzymes that have been found to be highly dynamic. Understanding conformational changes of heptosyltransferases are important to efficiently inhibiting them, but also contributing to the understanding of all GT-B enzymes. Finding new and smarter methods to inhibit bacterial growth is crucial, and the Heptosyltransferases may provide an important model for how to inhibit many GT-B enzymes. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessReview The Interactive Roles of Lipopolysaccharides and dsRNA/Viruses on Respiratory Epithelial Cells and Dendritic Cells in Allergic Respiratory Disorders: The Hygiene Hypothesis
Int. J. Mol. Sci. 2017, 18(10), 2219; https://doi.org/10.3390/ijms18102219
Received: 26 September 2017 / Revised: 18 October 2017 / Accepted: 19 October 2017 / Published: 23 October 2017
Cited by 2 | PDF Full-text (962 KB) | HTML Full-text | XML Full-text
Abstract
The original hygiene hypothesis declares “more infections in early childhood protect against later atopy”. According to the hygiene hypothesis, the increased incidence of allergic disorders in developed countries is explained by the decrease of infections. Epithelial cells and dendritic cells play key roles
[...] Read more.
The original hygiene hypothesis declares “more infections in early childhood protect against later atopy”. According to the hygiene hypothesis, the increased incidence of allergic disorders in developed countries is explained by the decrease of infections. Epithelial cells and dendritic cells play key roles in bridging the innate and adaptive immune systems. Among the various pattern-recognition receptor systems of epithelial cells and dendritic cells, including toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and others, TLRs are the key systems of immune response regulation. In humans, TLRs consist of TLR1 to TLR10. They regulate cellular responses through engagement with TLR ligands, e.g., lipopolysaccharides (LPS) acts through TLR4 and dsRNA acts through TLR3, but there are certain common components between these two TLR pathways. dsRNA activates epithelial cells and dendritic cells in different directions, resulting in allergy-related Th2-skewing tendency in epithelial cells, and Th1-skewing tendency in dendritic cells. The Th2-skewing effect by stimulation of dsRNA on epithelial cells could be suppressed by the presence of LPS above some threshold. When LPS level decreases, the Th2-skewing effect increases. It may be via these interrelated networks and related factors that LPS modifies the allergic responses and provides a plausible mechanism of the hygiene hypothesis. Several hygiene hypothesis-related phenomena, seemingly conflicting, are also discussed in this review, along with their proposed mechanisms. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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Open AccessReview Corneal Fibroblasts as Sentinel Cells and Local Immune Modulators in Infectious Keratitis
Int. J. Mol. Sci. 2017, 18(9), 1831; https://doi.org/10.3390/ijms18091831
Received: 31 July 2017 / Revised: 21 August 2017 / Accepted: 21 August 2017 / Published: 23 August 2017
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Abstract
The cornea serves as a barrier to protect the eye against external insults including microbial pathogens and antigens. Bacterial infection of the cornea often results in corneal melting and scarring that can lead to severe visual impairment. Not only live bacteria but also
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The cornea serves as a barrier to protect the eye against external insults including microbial pathogens and antigens. Bacterial infection of the cornea often results in corneal melting and scarring that can lead to severe visual impairment. Not only live bacteria but also their components such as lipopolysaccharide (LPS) of Gram-negative bacteria contribute to the development of inflammation and subsequent corneal damage in infectious keratitis. We describe the important role played by corneal stromal fibroblasts (activated keratocytes) as sentinel cells, immune modulators, and effector cells in infectious keratitis. Corneal fibroblasts sense bacterial infection through Toll-like receptor (TLR)–mediated detection of a complex of LPS with soluble cluster of differentiation 14 (CD14) and LPS binding protein present in tear fluid. The cells then initiate innate immune responses including the expression of chemokines and adhesion molecules that promote the recruitment of inflammatory cells necessary for elimination of the infecting bacteria. Infiltrated neutrophils are activated by corneal stromal collagen and release mediators that stimulate the production of pro–matrix metalloproteinases by corneal fibroblasts. Elastase produced by Pseudomonas aeruginosa (P. aeruginosa) activates these released metalloproteinases, resulting in the degradation of stromal collagen. The modulation of corneal fibroblast activation and of the interaction of these cells with inflammatory cells and bacteria is thus important to minimize corneal scarring during treatment of infectious keratitis. Pharmacological agents that are able to restrain such activities of corneal fibroblasts without allowing bacterial growth represent a potential novel treatment option for prevention of excessive scarring and tissue destruction in the cornea. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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