| First Author | Tesse A | Year | 2021 |
| Journal | Cells | Volume | 10 |
| Issue | 2 | PubMed ID | 33670755 |
| Mgi Jnum | J:323068 | Mgi Id | MGI:6806449 |
| Doi | 10.3390/cells10020435 | Citation | Tesse A, et al. (2021) Ablation of Aquaporin-9 Ameliorates the Systemic Inflammatory Response of LPS-Induced Endotoxic Shock in Mouse. Cells 10(2) |
| abstractText | 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-kappaB 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-kappaB signaling. The modulation of AQP9 expression/function may reveal to be useful in developing novel endotoxemia therapeutics. |
