Phospholipase C mediates therapeutic effects of WKYMVm against sepsis

• Published in: The Journal of immunology (1950) Vol. 196; no. 1_Supplement; pp. 131 - 131.15
• Main Authors: Kim, Hyung Sik, Lee, Sung Kyun, Park, Min Young, Kim, Ji Cheol, Bae, Yoe-Sik
• Format: Journal Article
• Language: English
• Published: 01-05-2016
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.131.15

Abstract
Sepsis is a serious life-threatening complicated clinical syndrome that results from a detrimental or damaging host reaction to infection. Previously we reported that an immune stimulating peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), strongly induced therapeutic effects against polymicrobial sepsis via formyl peptide receptor 2. In this study, we investigated the mechanism involved in WKYMVm-induced anti-septic activity focusing on phospholipase C (PLC). WKYMVm strongly stimulated mouse neutrophils, resulting in calcium increase which was completely blocked by a PLC-selective inhibitor (U-73122). We found that PLC-specific inhibitor U-73122 markedly blocked therapeutic effects of WKYMVm against sepsis. WKYMVm-induced inhibition of lung inflammation and lymphocyte apoptosis in cecal ligation and puncture sepsis model were markedly blocked by U-73122. We also found that WKYMVm-stimulated bactericidal activity and neutrophil migration to event area were also strongly inhibited by the PLC-selective inhibitor (U-73122). Taken together, we suggest that PLC enzymatic activity is essentially required for the therapeutic activity of WKYMVm against sepsis.