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Abstract: PO0633

Anti-Interleukin 22 Antibody Relieves Angiotensin II-Induced Renal Injury in Mice Through Inhibiting NLRP3 Inflammasome Activation

Session Information

  • CKD Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Author

  • Tang, Rong, Xiangya Hospital Central South University, Changsha, Hunan, China
Background

Interleukin-22 (IL-22) is considered as a proinflammatory cytokine and participates in the pathogenesis of inflammatory and autoimmune diseases. Previously, we found that serum IL-22 increased significantly in hypertensive renal damage patients, and IL-22 were positively correlated with renal damage. The aim of this study was to investigate whether anti-IL-22 antibody exerts renoprotective effect via inhibiting NLRP3 inflammasome activation in angiotensin II (Ang II) induced hypertensive renal damage in mice.

Methods

Ang II was infused subcutaneously at a rate of 1.5 mg/kg/d to C57BL/6 mice for 28 days to establish the hypertensive model. One day after modeling, mice were injected intraperitoneally every other day with saline, recombinant mouse IL-22 (rIL-22; 20 ug/kg), mouse anti-IL-22 monoclonal antibody (anti-IL-22 mAb; 1.25 ug/mouse) or isotype IgG. So mice were divided into 5 groups: control, Ang II, Ang II+rIL-22, Ang II+anti-IL-22, Ang II+IgG. 28 d after Ang II infusion, all mice were euthanized. Blood pressure, urinary albumin/creatinine ratio, serum creatinine (Scr) and renal histopathology were measured. NLRP3, cleaved caspase-1 and IL-1β in kidney were detected by western blot. Renal inflammatory factors were detected by ELISA, IL-22 and IL-22R1 in kidney were detected by immunohistochemistry, fibrotic related factors expression in kidney were evaluated by western blot.

Results

IL-22 and IL-22R1 Levels were elevated in kidney of Ang II-induced mice. Anti-IL-22 mAb therapy ameliorated proteinuria excretion, Scr and renal pathological damage in mice with established hypertensive renal injury. Blood pressure in Ang II-infused mice was also decreased after the treatment of anti-IL-22 mAb. In addition, anti-IL-22 mAb reduced NLRP3, cleaved caspase-1, IL-1β, TNF-α and IL-6 expression in kidney, along with inhibition of renal fibrotic related factors expression.

Conclusion

Anti-IL-22 antibody can reduce renal inflammation and fibrosis in Ang II-induced hypertensive mice, which may be through suppression of NLRP3/caspase-1/IL-1β pathway, suggesting it might exert therapeutic potential for the treatment of hypertensive renal injury.

IL-22, IL-22R expression and renal pathology

Funding

  • Government Support - Non-U.S.