TREM1 intervention does not affect renal pathology upon ischemia/reperfusion injury (TRAN1P.929)

Abstract

Abstract Rationale:Following transplantation, renal ischemia is a major cause of Acute Kidney injury(AKI). TREM1(Triggering receptor expressed on myeloid cells 1) is an innate immune receptor expressed on neutrophils and monocytes/macrophages, the most common cells infiltrating the kidney upon IR. TREM1 enhances Toll-like receptor (TLR)-induced inflammatory response in several models of infection and sterile inflammation.TREM1 inhibition reduced disease severity in mesenteric ischemia-reperfusion induced injury (IRI).We hypothesized that TREM1 intervention will also reduce renal IRI. Methods:Mice were subjected to renal IRI induced by occlusion of the renal artery for 25’ and reperfused for 24h. Mice were treated i.p. with different doses of LP17, LR12, TREM1 fusion protein and control peptides.Renal TREM1 protein expression and plasma sTREM1 were measured. TREM1 expression on circulating granulocyte and monocyte, renal function (creatinine, urea), damage (PASD) and inflammation (KC and LY6G-positive cell infiltration) were evaluated. Results:IRI was associated with increased renal and circulating TREM1 protein levels. TREM1 levels were similar on circulating granulocyte but decrease on monocyte upon IR. TREM1 intervention with LP17, LR12 and TREM1 fusion protein did not reduce renal dysfunction, injury or inflammation following IRI. Conclusion: The modulation of the TREM-1 pathway by means of synthetic peptides and fusion protein does not represent a useful tool to prevent renal IRI.