Next Article in Journal
Macrophages in Lung Injury, Repair, and Fibrosis
Previous Article in Journal
New Inhibitory Effects of Cilnidipine on Microglial P2X7 Receptors and IL-1β Release: An Involvement in its Alleviating Effect on Neuropathic Pain
Previous Article in Special Issue
Targeting Aquaporins in Novel Therapies for Male and Female Breast and Reproductive Cancers
Open AccessArticle

Ablation of Aquaporin-9 Ameliorates the Systemic Inflammatory Response of LPS-Induced Endotoxic Shock in Mouse

1
INSERM, CNRS, UNIV Nantes, l’institut du Thorax, 44007 Nantes, France
2
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “Aldo Moro”, 70125 Bari, Italy
3
Apoglyx AB, c/o Anyo AB, Ideon Science Park, 22370 Lund, Sweden
4
Division of Biochemistry and Structural Biology, Department of Chemistry, Lund University, 22100 Lund, Sweden
*
Authors to whom correspondence should be addressed.
Academic Editor: Sylviane Muller
Cells 2021, 10(2), 435; https://doi.org/10.3390/cells10020435
Received: 19 December 2020 / Revised: 14 February 2021 / Accepted: 15 February 2021 / Published: 18 February 2021
(This article belongs to the Special Issue Advances in Aquaporins)
Septic shock is the most severe complication of sepsis, being characterized by a systemic inflammatory response following bacterial infection, leading to multiple organ failure and dramatically high mortality. Aquaporin-9 (AQP9), a membrane channel protein mainly expressed in hepatocytes and leukocytes, has been recently associated with inflammatory and infectious responses, thus triggering strong interest as a potential target for reducing septic shock-dependent mortality. Here, we evaluated whether AQP9 contributes to murine systemic inflammation during endotoxic shock. Wild type (Aqp9+/+; WT) and Aqp9 gene knockout (Aqp9−/−; KO) male mice were submitted to endotoxic shock by i.p. injection of lipopolysaccharide (LPS; 40 mg/kg) and the related survival times were followed during 72 h. The electronic paramagnetic resonance and confocal microscopy were employed to analyze the nitric oxide (NO) and superoxide anion (O2) production, and the expression of inducible NO-synthase (iNOS) and cyclooxigenase-2 (COX-2), respectively, in the liver, kidney, aorta, heart and lung of the mouse specimens. LPS-treated KO mice survived significantly longer than corresponding WT mice, and 25% of the KO mice fully recovered from the endotoxin treatment. The LPS-injected KO mice showed lower inflammatory NO and O2 productions and reduced iNOS and COX-2 levels through impaired NF-κB p65 activation in the liver, kidney, aorta, and heart as compared to the LPS-treated WT mice. Consistent with these results, the treatment of FaO cells, a rodent hepatoma cell line, with the AQP9 blocker HTS13268 prevented the LPS-induced increase of inflammatory NO and O2. A role for AQP9 is suggested in the early acute phase of LPS-induced endotoxic shock involving NF-κB signaling. The modulation of AQP9 expression/function may reveal to be useful in developing novel endotoxemia therapeutics. View Full-Text
Keywords: membrane transport; hydrogen peroxide; peroxiporins; aquaglyceroporins; LPS; sepsis; inflammation; nitric oxide; superoxide anion; NF-κB pathway; redox signaling; drug targets membrane transport; hydrogen peroxide; peroxiporins; aquaglyceroporins; LPS; sepsis; inflammation; nitric oxide; superoxide anion; NF-κB pathway; redox signaling; drug targets
Show Figures

Figure 1

MDPI and ACS Style

Tesse, A.; Gena, P.; Rützler, M.; Calamita, G. Ablation of Aquaporin-9 Ameliorates the Systemic Inflammatory Response of LPS-Induced Endotoxic Shock in Mouse. Cells 2021, 10, 435. https://doi.org/10.3390/cells10020435

AMA Style

Tesse A, Gena P, Rützler M, Calamita G. Ablation of Aquaporin-9 Ameliorates the Systemic Inflammatory Response of LPS-Induced Endotoxic Shock in Mouse. Cells. 2021; 10(2):435. https://doi.org/10.3390/cells10020435

Chicago/Turabian Style

Tesse, Angela; Gena, Patrizia; Rützler, Michael; Calamita, Giuseppe. 2021. "Ablation of Aquaporin-9 Ameliorates the Systemic Inflammatory Response of LPS-Induced Endotoxic Shock in Mouse" Cells 10, no. 2: 435. https://doi.org/10.3390/cells10020435

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop