Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases

Topic Information

Dear Colleagues,

Chronic respiratory disorders, such as lung cancer, chronic obstructive pulmonary disease (COPD), lung fibrosis, asthma, or pulmonary hypertension (PH), are responsible for a significant portion of deaths worldwide. Likewise, allergic conditions other than asthma, for instance, allergic rhinitis, atopic dermatitis, or food allergy, lead to a substantial worsening of health-related quality of life in patients and considerable socio-economic burden to the affected families and healthcare systems. Various mechanisms and pathways, including those related to innate or adaptive immunity and/or immunometabolism or coagulation, underlie the pathogenesis of chronic diseases of the airways and allergic disorders. In recent decades, it has become apparent that the interaction between genetic background and beneficial (e.g., some diets) or adverse (e.g., pollution) environmental influences, frequently epigenetically mediated, plays a fundamental etiological role in the origins and progression of chronic lung and allergic diseases. Furthermore, current literature reports dysregulation of developmental pathways in chronic lung diseases and thereby suggests the importance of homeostatic mechanisms for lung structural and functional integrity in adult life. Other studies focus on the interactions between lung, skin, and gut microbiota, including bacteria, fungi, parasites, viruses, and archaea, and their influence on respiratory and allergic diseases. Despite considerable progress in our understanding of the mechanistic basis of those disorders achieved in recent years, a lot remains to be done to achieve substantial diagnostic and therapeutic advances in patient management. Therefore, the scope of this Topic focuses on recent findings in molecular and cellular pathogenesis, diagnostic methods, and treatment and prevention of chronic inflammatory lung and allergic diseases.

Prof. Dr. Malgorzata Wygrecka
Dr. Daniel P. Potaczek
Dr. Bilal Alashkar Alhamwe
Dr. Stefan Hadžić
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Allergies allergies	-	-	2021	40.9 Days	CHF 1000
BioChem biochem	-	-	2021	21.7 Days	CHF 1000
Biomedicines biomedicines	3.9	5.2	2013	14.6 Days	CHF 2600
Cells cells	5.1	9.9	2012	17 Days	CHF 2700
Current Issues in Molecular Biology cimb	2.8	2.9	1999	15.8 Days	CHF 2200
Diagnostics diagnostics	3.0	4.7	2011	20.3 Days	CHF 2600
International Journal of Molecular Sciences ijms	4.9	8.1	2000	16.8 Days	CHF 2900

Preprints.org is a multidisciplinary platform offering a preprint service designed to facilitate the early sharing of your research. It supports and empowers your research journey from the very beginning.

MDPI Topics is collaborating with Preprints.org and has established a direct connection between MDPI journals and the platform. Authors are encouraged to take advantage of this opportunity by posting their preprints at Preprints.org prior to publication:

1. Share your research immediately: disseminate your ideas prior to publication and establish priority for your work.
2. Safeguard your intellectual contribution: Protect your ideas with a time-stamped preprint that serves as proof of your research timeline.
3. Boost visibility and impact: Increase the reach and influence of your research by making it accessible to a global audience.
4. Gain early feedback: Receive valuable input and insights from peers before submitting to a journal.
5. Ensure broad indexing: Web of Science (Preprint Citation Index), Google Scholar, Crossref, SHARE, PrePubMed, Scilit and Europe PMC.

Published Papers (12 papers)

Order results

Content type Publication Date

Result details

Normal Extended Compact

Journals

All Allergies BioChem Biomedicines Cells CIMB Diagnostics IJMS

Show export options expand_more Show export options expand_less

Select all

Export citation of selected articles as:

Plain Text BibTeX BibTeX (without abstracts) Endnote Endnote (without abstracts) Tab-delimited RIS

Error

Oops... you haven't selected anything for export.

Ok

clear

18 pages, 3016 KiB  

Open AccessArticle

IL-20 Cytokines Are Involved in the Repair of Airway Epithelial Barrier: Implication in Exposure to Cigarette Smoke and in COPD Pathology

by Olivia Barada, Sophie Salomé-Desnoulez, Fahima Madouri, Gaëtan Deslée, Christelle Coraux, Philippe Gosset and Muriel Pichavant

Cells 2023, 12(20), 2464; https://doi.org/10.3390/cells12202464 - 16 Oct 2023

Cited by 3 | Viewed by 1924

Abstract

Background: Dysregulated inflammation as seen in chronic obstructive pulmonary disease (COPD) is associated with impaired wound healing. IL-20 cytokines are known to be involved in wound healing processes. The purpose of this study was to use ex vivo and in vitro approaches mimicking [...] Read more.

Background: Dysregulated inflammation as seen in chronic obstructive pulmonary disease (COPD) is associated with impaired wound healing. IL-20 cytokines are known to be involved in wound healing processes. The purpose of this study was to use ex vivo and in vitro approaches mimicking COPD to evaluate the potential modulatory role of interleukin-20 (IL-20) on the inflammatory and healing responses to epithelial wounding. Methods: The expression of IL-20 cytokines and their receptors was investigated in lung-derived samples collected from non-COPD and COPD patients, from mice chronically exposed to cigarette smoke and from airway epithelial cells from humans and mice exposed in vitro to cigarette smoke. To investigate the role of IL-20 cytokines in wound healing, experiments were performed using a blocking anti-IL-20Rb antibody. Results: Of interest, IL-20 cytokines and their receptors were expressed in bronchial mucosa, especially on airway epithelial cells. Their expression correlated with the disease severity. Blocking these cytokines in a COPD context improved the repair processes after a lesion induced by scratching the epithelial layer. Conclusions: Collectively, this study highlights the implication of IL-20 cytokines in the repair of the airway epithelium and in the pathology of COPD. IL-20 subfamily cytokines might provide therapeutic benefit for patients with COPD to improve epithelial healing. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Graphical abstract

19 pages, 1444 KiB  

Open AccessReview

Human Lung Organoids—A Novel Experimental and Precision Medicine Approach

by Laura Kühl, Pauline Graichen, Nele von Daacke, Anne Mende, Malgorzata Wygrecka, Daniel P. Potaczek, Sarah Miethe and Holger Garn

Cells 2023, 12(16), 2067; https://doi.org/10.3390/cells12162067 - 15 Aug 2023

Cited by 18 | Viewed by 4791

Abstract

The global burden of respiratory diseases is very high and still on the rise, prompting the need for accurate models for basic and translational research. Several model systems are currently available ranging from simple airway cell cultures to complex tissue-engineered lungs. In recent [...] Read more.

The global burden of respiratory diseases is very high and still on the rise, prompting the need for accurate models for basic and translational research. Several model systems are currently available ranging from simple airway cell cultures to complex tissue-engineered lungs. In recent years, human lung organoids have been established as highly transferrable three-dimensional in vitro model systems for lung research. For acute infectious and chronic inflammatory diseases as well as lung cancer, human lung organoids have opened possibilities for precise in vitro research and a deeper understanding of mechanisms underlying lung injury and regeneration. Human lung organoids from induced pluripotent stem cells or from adult stem cells of patients’ samples introduce tools for understanding developmental processes and personalized medicine approaches. When further state-of-the-art technologies and protocols come into use, the full potential of human lung organoids can be harnessed. High-throughput assays in drug development, gene therapy, and organoid transplantation are current applications of organoids in translational research. In this review, we emphasize novel approaches in translational and personalized medicine in lung research focusing on the use of human lung organoids. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Figure 1

16 pages, 4195 KiB  

Open AccessArticle

PAI-1 Regulation of p53 Expression and Senescence in Type II Alveolar Epithelial Cells

by Tapasi Rana, Chunsun Jiang, Sami Banerjee, Nengjun Yi, Jaroslaw W. Zmijewski, Gang Liu and Rui-Ming Liu

Cells 2023, 12(15), 2008; https://doi.org/10.3390/cells12152008 - 5 Aug 2023

Cited by 8 | Viewed by 2762

Abstract

Cellular senescence contributes importantly to aging and aging-related diseases, including idiopathic pulmonary fibrosis (IPF). Alveolar epithelial type II (ATII) cells are progenitors of alveolar epithelium, and ATII cell senescence is evident in IPF. Previous studies from this lab have shown that increased expression [...] Read more.

Cellular senescence contributes importantly to aging and aging-related diseases, including idiopathic pulmonary fibrosis (IPF). Alveolar epithelial type II (ATII) cells are progenitors of alveolar epithelium, and ATII cell senescence is evident in IPF. Previous studies from this lab have shown that increased expression of plasminogen activator inhibitor 1 (PAI-1), a serine protease inhibitor, promotes ATII cell senescence through inducing p53, a master cell cycle repressor, and activating p53-p21-pRb cell cycle repression pathway. In this study, we further show that PAI-1 binds to proteasome components and inhibits proteasome activity and p53 degradation in human lung epithelial A549 cells and primary mouse ATII cells. This is associated with a senescence phenotype of these cells, manifested as increased p53 and p21 expression, decreased phosphorylated retinoblastoma protein (pRb), and increased senescence-associated beta-galactose (SA-β-gal) activity. Moreover, we find that, although overexpression of wild-type PAI-1 (wtPAI-1) or a secretion-deficient, mature form of PAI-1 (sdPAI-1) alone induces ATII cell senescence (increases SA-β-gal activity), only wtPAI-1 induces p53, suggesting that the premature form of PAI-1 is required for the interaction with the proteasome. In summary, our data indicate that PAI-1 can bind to proteasome components and thus inhibit proteasome activity and p53 degradation in ATII cells. As p53 is a master cell cycle repressor and PAI-1 expression is increased in many senescent cells, the results from this study will have a significant impact not only on ATII cell senescence/lung fibrosis but also on the senescence of other types of cells in different diseases. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 424 KiB)

18 pages, 5300 KiB  

Open AccessArticle

Nutritional Provision of Iron Complexes by the Major Allergen Alt a 1 to Human Immune Cells Decreases Its Presentation

by Aila Fakhimahmadi, Ilir Hasanaj, Gerlinde Hofstetter, Clara Pogner, Markus Gorfer, Markus Wiederstein, Nathalie Szepannek, Rodolfo Bianchini, Zdenek Dvorak, Sebastian A. Jensen, Markus Berger, Erika Jensen-Jarolim, Karin Hufnagl and Franziska Roth-Walter

Int. J. Mol. Sci. 2023, 24(15), 11934; https://doi.org/10.3390/ijms241511934 - 25 Jul 2023

Cited by 4 | Viewed by 2361

Abstract

Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to [...] Read more.

Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron–quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations. Recombinant Alt a 1 was generated, and binding ability, as well as secondary and quaternary structure, assessed by UV-VIS, CD, and DLS spectroscopy. Proteolytic functions were determined by casein and gelatine zymography. Uptake of empty apo– or ligand-filled holoAlt a 1 were assessed in human monocytic THP1 cells under the presence of dynamin and clathrin-inhibitors, activation of the Arylhydrocarbon receptor (AhR) using the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for phenotypic changes in monocytes by flow cytometry. Alt a 1 bound strongly to FeQ2 as a tetramer with calculated K_d values reaching pico-molar levels and surpassing affinities to quercetin alone by a factor of 5000 for the tetramer. apoAlt a 1 but not holoAlta 1 showed low enzymatic activity against casein as a hexamer and gelatin as a trimer. Uptake of apo– and holo–Alt a 1 occurred partly clathrin-dependent, with apoAlt a 1 decreasing labile iron in THP1 cells and holoAlt a 1 facilitating quercetin-dependent AhR activation. In human PBMCs uptake of holoAlt a 1 but not apoAlt a 1 significantly decreased the surface expression of the costimulatory CD86, but also of HLADR, thereby reducing effective antigen presentation. We show here for the first time that the presence of nutritional iron complexes, such as FeQ2, significantly alters the function of Alt a 1 and dampens the human immune response, thereby supporting the notion that Alt a 1 only becomes immunogenic under nutritional deprivation. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)
(This article belongs to the Section Molecular Biology)

►▼ Show Figures

Figure 1

19 pages, 5067 KiB  

Open AccessArticle

An In Vitro Alveolar Model Allows for the Rapid Assessment of Particles for Respiratory Sensitization Potential

by Matthew Gibb and Christie M. Sayes

Int. J. Mol. Sci. 2023, 24(12), 10104; https://doi.org/10.3390/ijms241210104 - 14 Jun 2023

Cited by 3 | Viewed by 2153

Abstract

Dust, both industrial and household, contains particulates that can reach the most distal aspects of the lung. Silica and nickel compounds are two such particulates and have known profiles of poor health outcomes. While silica is well-characterized, nickel compounds still need to be [...] Read more.

Dust, both industrial and household, contains particulates that can reach the most distal aspects of the lung. Silica and nickel compounds are two such particulates and have known profiles of poor health outcomes. While silica is well-characterized, nickel compounds still need to be fully understood for their potential to cause long-term immune responses in the lungs. To assess these hazards and decrease animal numbers used in testing, investigations that lead to verifiable in vitro methods are needed. To understand the implications of these two compounds reaching the distal aspect of the lungs, the alveoli, an architecturally relevant alveolar model consisting of epithelial cells, macrophages, and dendritic cells in a maintained submerged system, was utilized for high throughput testing. Exposures include crystalline silica (SiO₂) and nickel oxide (NiO). The endpoints measured included mitochondrial reactive oxygen species and cytostructural changes assessed via confocal laser scanning microscopy; cell morphology evaluated via scanning electron microscopy; biochemical reactions assessed via protein arrays; transcriptome assessed via gene arrays, and cell surface activation markers evaluated via flow cytometry. The results showed that, compared to untreated cultures, NiO increased markers for dendritic cell activation, trafficking, and antigen presentation; oxidative stress and cytoskeletal changes, and gene and cytokine expression of neutrophil and other leukocyte chemoattractants. The chemokines and cytokines CCL3, CCL7, CXCL5, IL-6, and IL-8 were identified as potential biomarkers of respiratory sensitization. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 238 KiB)

15 pages, 18269 KiB  

Open AccessArticle

Calcitriol, an Active Form of Vitamin D3, Mitigates Skin Barrier Dysfunction in Atopic Dermatitis NC/Nga Mice

by Yoshie Umehara, Juan Valentin Trujillo-Paez, Hainan Yue, Ge Peng, Hai Le Thanh Nguyen, Ko Okumura, Hideoki Ogawa and François Niyonsaba

Int. J. Mol. Sci. 2023, 24(11), 9347; https://doi.org/10.3390/ijms24119347 - 27 May 2023

Cited by 4 | Viewed by 4240

Abstract

Atopic dermatitis and psoriasis are prevalent chronic inflammatory skin diseases that are characterized by dysfunctional skin barriers and substantially impact patients’ quality of life. Vitamin D3 regulates immune responses and keratinocyte differentiation and improves psoriasis symptoms; however, its effects on atopic dermatitis remain [...] Read more.

Atopic dermatitis and psoriasis are prevalent chronic inflammatory skin diseases that are characterized by dysfunctional skin barriers and substantially impact patients’ quality of life. Vitamin D3 regulates immune responses and keratinocyte differentiation and improves psoriasis symptoms; however, its effects on atopic dermatitis remain unclear. Here, we investigated the effects of calcitriol, an active form of vitamin D3, on an NC/Nga mouse model of atopic dermatitis. We observed that the topical application of calcitriol decreased the dermatitis scores and epidermal thickness of NC/Nga mice with atopic dermatitis compared to untreated mice. In addition, both stratum corneum barrier function as assessed by the measurement of transepidermal water loss and tight junction barrier function as evaluated by biotin tracer permeability assay were improved following calcitriol treatment. Moreover, calcitriol treatment reversed the decrease in the expression of skin barrier-related proteins and decreased the expression of inflammatory cytokines such as interleukin (IL)-13 and IL-33 in mice with atopic dermatitis. These findings suggest that the topical application of calcitriol might improve the symptoms of atopic dermatitis by repairing the dysfunctional epidermal and tight junction barriers. Our results suggest that calcitriol might be a viable therapeutic agent for the treatment of atopic dermatitis in addition to psoriasis. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)
(This article belongs to the Section Molecular Biology)

►▼ Show Figures

Figure 1

18 pages, 3803 KiB  

Open AccessArticle

Circulating Regulatory T Cell Subsets in Patients with Sarcoidosis

by Igor Kudryavtsev, Yulia Zinchenko, Anna Starshinova, Maria Serebriakova, Anna Malkova, Tatiana Akisheva, Dmitriy Kudlay, Anzhela Glushkova, Piotr Yablonskiy and Yehuda Shoenfeld

Diagnostics 2023, 13(8), 1378; https://doi.org/10.3390/diagnostics13081378 - 10 Apr 2023

Cited by 10 | Viewed by 3053

Abstract

Over recent years, many researchers have supported the autoimmune theory of sarcoidosis. The presence of uncontrolled inflammatory response on local and system levels in patients with sarcoidosis did not define that the immunoregulatory mechanisms could be affected. The aim of this study was [...] Read more.

Over recent years, many researchers have supported the autoimmune theory of sarcoidosis. The presence of uncontrolled inflammatory response on local and system levels in patients with sarcoidosis did not define that the immunoregulatory mechanisms could be affected. The aim of this study was to evaluate the distribution and the disturbance circulating Treg cell subsets in the peripheral blood in patients with sarcoidosis. Materials and methods: A prospective comparative study was performed in 2016–2018 (34 patients with sarcoidosis (men (67.6%), women (32.3%)) were examined). Healthy subjects—the control group (n = 40). The diagnosis of pulmonary sarcoidosis was performed according to the standard criteria. We used two ten-color combinations of antibodies for Treg immunophenotyping. The first one contained CD39–FITC, CD127–PE, CCR4–PE/Dazzle™ 594, CD25–PC5.5, CD161–PC7, CD4–APC, CD8–APC–AF700, CD3–APC/Cy7, HLA–DR–PacBlue, and CD45 RA–BV 510™, while the second consisted of CXCR3–Alexa Fluor 488, CD25–РЕ, CXCR5–РЕ/Dazzle™ 594, CCR4–PerСP/Сy5.5, CCR6–РЕ/Cy7, CD4–АPC, CD8 АPC–AF700, CD3–АPC/Cy7, CCR7–BV 421, and CD45 RA–BV 510. The flow cytometry data were analyzed by using Kaluza software v2.3. A statistical analysis was performed with Statistica 7.0 and GraphPad Prism 8 software packages. Results of the study: Primarily, we found that patients with sarcoidosis had decreased absolute numbers of Treg cells in circulation. We noted that the level of CCR7-expressing Tregs decreased in patients with sarcoidosis vs. the control group (65.55% (60.08; 70.60) vs. 76.93% (69.59; 79.86) with p < 0.001). We noticed that the relative numbers of CD45RA–CCR7+ Tregs decreased in patients with sarcoidosis (27.11% vs. 35.43%, p < 0.001), while the frequency of CD45 RA–CCR7– and CD45RA+ CCR7– Tregs increased compared to the control group (33.3% vs. 22.73% and 0.76% vs. 0.51% with p < 0.001 and p = 0.028, respectively). CXCR3-expressing Treg cell subsets—Th1-like CCR60078CXCR3+ Tregs and Th17.1-like CCR6+ CXCR3+ Tregs—significantly increased in patients with sarcoidosis vs. the control group (14.4% vs. 10.5% with p < 0.01 and 27.9% vs. 22.8% with p < 0.01, respectively). Furthermore, the levels of peripheral blood EM Th17-like Tregs significantly decreased in the sarcoidosis group vs. the control group (36.38% vs. 46.70% with p < 0.001). Finally, we found that CXCR5 expression was increased in CM Tregs cell subsets in patients with sarcoidosis. Conclusions: Our data indicated a decrease in circulating Tregs absolute numbers and several alterations in Treg cell subsets. Moreover, our results highlight the presence of increased levels of CM CXCR5+ follicular Tregs in the periphery that could be linked with the imbalance of follicular Th cell subsets and alterations in B cell, based on the immune response. The balance between the two functionally distinct Treg cell populations—Th1-like and Th17-like Tregs—could be used in sarcoidosis diagnosis and the determination of prognosis and disease outcomes. Furthermore, we want to declare that analysis of Treg numbers of phenotypes could fully characterize their functional activity in peripherally inflamed tissues. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Figure 1

24 pages, 1443 KiB  

Open AccessReview

Blood-Based Biomarkers for Eosinophilic Esophagitis and Concomitant Atopic Diseases: A Look into the Potential of Extracellular Vesicles

by Elena Grueso-Navarro, Pilar Navarro, Emilio J. Laserna-Mendieta, Alfredo J. Lucendo and Laura Arias-González

Int. J. Mol. Sci. 2023, 24(4), 3669; https://doi.org/10.3390/ijms24043669 - 11 Feb 2023

Cited by 14 | Viewed by 5382

Abstract

Eosinophilic esophagitis (EoE) is a chronic, Th2-inflammatory disease of the esophagus that can severely affect food intake. Currently, diagnosis and assessing response to treatment of EoE is highly invasive and requires endoscopy with esophageal biopsies. Finding non-invasive and accurate biomarkers is important for [...] Read more.

Eosinophilic esophagitis (EoE) is a chronic, Th2-inflammatory disease of the esophagus that can severely affect food intake. Currently, diagnosis and assessing response to treatment of EoE is highly invasive and requires endoscopy with esophageal biopsies. Finding non-invasive and accurate biomarkers is important for improving patient well-being. Unfortunately, EoE is usually accompanied by other atopies, which make it difficult to identify specific biomarkers. Providing an update of circulating EoE biomarkers and concomitant atopies is therefore timely. This review summarizes the current knowledge in EoE blood biomarkers and two of its most common comorbidities, bronchial asthma (BA) and atopic dermatitis (AD), focusing on dysregulated proteins, metabolites, and RNAs. It also revises the current knowledge on extracellular vesicles (EVs) as non-invasive biomarkers for BA and AD, and concludes with the potential use of EVs as biomarkers in EoE. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 2194 KiB)

21 pages, 1293 KiB  

Open AccessArticle

SNPs Sets in Codifying Genes for Xenobiotics-Processing Enzymes Are Associated with COPD Secondary to Biomass-Burning Smoke

by Enrique Ambrocio-Ortiz, Gloria Pérez-Rubio, Alejandra Ramírez-Venegas, Rafael de Jesús Hernández-Zenteno, Juan Carlos Fernández-López, María Elena Ramírez-Díaz, Filiberto Cruz-Vicente, María de Lourdes Martínez-Gómez, Raúl Sansores, Julia Pérez-Ramos and Ramcés Falfán-Valencia

Curr. Issues Mol. Biol. 2023, 45(2), 799-819; https://doi.org/10.3390/cimb45020053 - 17 Jan 2023

Cited by 2 | Viewed by 2735

Abstract

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; the main risk factors associated with the suffering are tobacco smoking (TS) and chronic exposure to biomass-burning smoke (BBS). Different biological pathways have been associated with COPD, especially xenobiotic or [...] Read more.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; the main risk factors associated with the suffering are tobacco smoking (TS) and chronic exposure to biomass-burning smoke (BBS). Different biological pathways have been associated with COPD, especially xenobiotic or drug metabolism enzymes. This research aims to identify single nucleotide polymorphisms (SNPs) profiles associated with COPD from two expositional sources: tobacco smoking and BBS. One thousand-five hundred Mexican mestizo subjects were included in the study and divided into those exposed to biomass-burning smoke and smokers. Genome-wide exome genotyping was carried out using Infinium Exome-24 kit arrays v. 1.2. Data quality control was conducted using PLINK 1.07. For clinical and demographic data analysis, Rstudio was used. Eight SNPs were found associated with COPD secondary to TS and seven SNPs were conserved when data were analyzed by genotype. When haplotype analyses were carried out, five blocks were predicted. In COPD secondary to BBS, 24 SNPs in MGST3 and CYP family genes were associated. Seven blocks of haplotypes were associated with COPD-BBS. SNPs in the ARNT2 and CYP46A1 genes are associated with COPD secondary to TS, while in the BBS comparison, SNPs in CYP2C8, CYP2C9, MGST3, and MGST1 genes were associated with increased COPD risk. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Figure 1

14 pages, 1420 KiB  

Open AccessReview

Anti-Oxidant and Pro-Oxidant Effects of Peroxiredoxin 6: A Potential Target in Respiratory Diseases

by Wenhui Jia, Chunling Dong and Bo Li

Cells 2023, 12(1), 181; https://doi.org/10.3390/cells12010181 - 1 Jan 2023

Cited by 11 | Viewed by 3223

Abstract

Peroxiredoxin 6 (PRDX6) is widely distributed in several organs, especially the lungs. The role of PRDX6 in oxidative stress is controversial and even contradictory, as indicated by research conducted over the past 20 years. PRDX6 has anti-oxidant or pro-oxidant effects on oxidative stress [...] Read more.

Peroxiredoxin 6 (PRDX6) is widely distributed in several organs, especially the lungs. The role of PRDX6 in oxidative stress is controversial and even contradictory, as indicated by research conducted over the past 20 years. PRDX6 has anti-oxidant or pro-oxidant effects on oxidative stress in different diseases. It can even exhibit both anti-oxidant and pro-oxidant effects in the same disease. These findings are attributed to the fact that PRDX6 is a multifunctional enzyme. The peroxidase and phospholipase A2 activity of PRDX6 is closely related to its anti-oxidant and pro-oxidant effects, which leads to the conflicting regulatory effects of PRDX6 on oxidative stress in respiratory diseases. Moreover, PRDX6 interacts with multiple redox signaling pathways to interfere with cell proliferation and apoptosis. PRDX6 has become a new target in respiratory disease research due to its important regulatory role in oxidative stress. In this paper, the role of PRDX6 in oxidative stress in respiratory diseases and the research progress in targeting PRDX6 are reviewed. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 270 KiB)

15 pages, 3170 KiB  

Open AccessArticle

Lactoferrin Ameliorates Ovalbumin-Induced Asthma in Mice through Reducing Dendritic-Cell-Derived Th2 Cell Responses

by Chi-Chien Lin, Kai-Cheng Chuang, Shih-Wei Chen, Ya-Hsuan Chao, Chih-Ching Yen, Shang-Hsun Yang, Wei Chen, Kuang-Hsi Chang, Yu-Kang Chang and Chuan-Mu Chen

Int. J. Mol. Sci. 2022, 23(22), 14185; https://doi.org/10.3390/ijms232214185 - 16 Nov 2022

Cited by 14 | Viewed by 3951

Abstract

Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, [...] Read more.

Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, and antitumoral activities. LF has been shown to function in immunoregulatory activities in ovalbumin (OVA)-induced delayed type hypersensitivity (DTH) in mice. Hence, the purpose of this study was to investigate the roles of LF in AHR and the functions of dendritic cells (DCs) and Th2-related responses in asthma. Twenty 8-week-old male BALB/c mice were divided into normal control (NC), ovalbumin (OVA)-sensitized, and OVA-sensitized with low dose of LF (100 mg/kg) or high dose of LF (300 mg/kg) treatment groups. The mice were challenged by intranasal instillation with 5% OVA on the 21st to 27th day after the start of the sensitization period. The AHR, cytokines in bronchoalveolar lavage fluid, and pulmonary histology of each mouse were measured. Serum OVA-specific IgE and IgG1 and OVA-specific splenocyte responses were further detected. The results showed that LF exhibited protective effects in ameliorating AHR, as well as lung inflammation and damage, in reducing the expression of Th2 cytokines and the secretion of allergen-specific antibodies, in influencing the functions of DCs, and in decreasing the level of Th2 immune responses in a BALB/c mouse model of OVA-induced allergic asthma. Importantly, we demonstrated that LF has practical application in reducing DC-induced Th2 cell responses in asthma. In conclusion, LF exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma. These results suggest that LF may act as a supplement to prevent asthma-induced lung injury and provide an additional agent for reducing asthma severity. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 267 KiB)

15 pages, 2560 KiB  

Open AccessArticle

K63 Ubiquitination of P21 Can Facilitate Pellino-1 in the Context of Chronic Obstructive Pulmonary Disease and Lung Cellular Senescence

by Jia-Hui Ma, Yi-Ting Zhang, Lu-Ping Wang, Qing-Yu Sun, Hao Zhang, Jian-Jiang Li, Ning-Ning Han, Yao-Yao Zhu, Xiao-Yu Xie and Xia Li

Cells 2022, 11(19), 3115; https://doi.org/10.3390/cells11193115 - 3 Oct 2022

Cited by 6 | Viewed by 2620

Abstract

Chronic obstructive pulmonary diseases (COPD) is a kind of age-related, airflow-obstruction disease mostly caused by cigarette smoke. However, the relationship between COPD and lung cellular senescence is still not fully understood. Here, we found silencing Pellino-1 could inhibit the protein level of P21. [...] Read more.

Chronic obstructive pulmonary diseases (COPD) is a kind of age-related, airflow-obstruction disease mostly caused by cigarette smoke. However, the relationship between COPD and lung cellular senescence is still not fully understood. Here, we found silencing Pellino-1 could inhibit the protein level of P21. Then, through constructing cell lines expressed ubiquitin-HA, we found that the E3 ubiquitin ligase Pellino-1 could bind to senescence marker p21 and modify p21 by K63-site ubiquitination by co-IP assays. Furthermore, we found that p21-mediated lung cellular senescence could be inhibited by silencing Pellino-1 in a D-galactose senescence mice model. Moreover, by constructing a COPD mouse model with shPellino-1 adenovirus, we found that silencing Pellino-1 could inhibit COPD and inflammation via reduction of SASPs regulated by p21. Taken together, our study findings elucidated that silencing E3 ligase Pellino-1 exhibits therapeutic potential for treatment to attenuate the progression of lung cellular senescence and COPD. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Chronic Respiratory and Allergic Diseases)

►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less

Select all

Export citation of selected articles as:

Plain Text BibTeX BibTeX (without abstracts) Endnote Endnote (without abstracts) Tab-delimited RIS

 

Error

Oops... you haven't selected anything for export.

Ok

clear

Displaying articles 1-12