MO330ACTIVATION OF Β2 ADRENERGIC RECEPTOR SIGNALING IN MACROPHAGES BLOCKS SYSTEMIC INFLAMMATION AND PROTECTS AGAINST RENAL ISCHEMIA/REPERFUSION INJURY

Abstract Background and Aims The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of signaling in inflammatory diseases is still unclear because it varies according to disease situation responsible types. Here, we focused on macrophages sought determine its roles lipopolysaccharide (LPS)-induced systemic inflammation renal ischemia/reperfusion injury (IRI). Method In vitro, RAW 264.7 cells murine peritoneal were used effects β2 adrenergic receptor (Adrb2) LPS-induced proinflammatory cytokine (tumor necrosis factor-α; TNF-α) production. We also identified critical gene that mediates anti-inflammatory effect Adrb2 by RNA-sequencing. vivo, examined salbutamol (a selective agonist) IRI. involvement macrophage was confirmed macrophage-specific conditional knockout (cKO) mice adoptive transfer salbutamol-treated macrophages. performed single-cell RNA sequencing tissue analyze renoprotective detail. Results norepinephrine, a neurotransmitter, suppressed TNF-α production This induced reversed butoxamine antagonist) dose-dependent manner, indicating importance this process. these revealed T-cell immunoglobulin mucin-3 (Tim3) expressions upregulated activation signaling, which partially mediated phenotypic alteration administration mitigated protected against IRI; protection cKO mice. Adoptive IRI (Figure 1). Single-cell associated with accumulation Tim3-expressing tissue. Conclusion induces alterations via induction Tim3 expressions, blocks protects