#5165 STING CONTRIBUTES TO LPS-INDUCED TUBULAR INFLAMMATION BY ACTIVATING IRE1/XBP1 PATHWAY IN ACUTE KIDNEY INJURY

Abstract Background and Aims Innate immunity inflammation were recognized as the key factors for progression of acute kidney injury (AKI) induced by lipopolysaccharide (LPS). Stimulator interferon genes (STING) has emerged a critical component innate immune inflammatory responses. This study aimed to explore role STING in LPS-induced tubular AKI. Method 1. The AKI mice models intraperitoneal injection LPS. Mice randomly divided into CTL group, LPS 24 h group 48 group: (1) protein expression tubules was detected IHC staining; (2) cortices WB. 2. tubule-specific knockout (STING-cKO) generated. Then WT STING-cKO WT+LPS STING-cKO+LPS Blood samples urine collected Scr, BUN ACR measurement; Tubular pathological changes PAS (3) Inflammatory cell infiltration IF (4) Pro-inflammatory cytokines’ mRNA level QPCR; (5) IRE1, XBP1, IL-1β IL-18 3. HK2 cells si-STING (STING siRNA) LPS+si-STING Ad-IRE1 (IRE1 overexpression plasmid) si-STING+ LPS+ IL-1β, Results activated from mice. significantly suppressed renal dysfunction, changes, IRE1/XBP1 pathway activation. 3.IRE1 promoted LPS-activated cells’ inflammation, even though silenced. Conclusion contributes activating pathway. Targeting may be promising therapeutic strategy preventing septic