MO scavenger receptors and mediators in rodent models of intestinal and hepatic inflammation

Macrophages (MO) within tissues fulfil predominately a homeostatic role by regulating the local and systemic milieu through diverse plasma membrane receptors and varied secretory products. In this study we evaluated the roles of different MO scavenger receptor (MSR) and MO secreted mediators, including Group IIA secretory phospholipase A2 (sPLA2), nitric oxide (NO), and interleukin-10 (IL-10), in different rodent models of inflammation.; The role of Group IIA sPLA2 in IBD has caused controversy in recent years. Here we demonstrate that MO-derived Group IIA sPLA 2 protects against, rather than promote, colitis in a mouse model of colitis. This may be caused by the functional coupling between Group IIA sPLA 2 and its down stream enzyme (cyclooxygenase-2[COX-2]) in increasing the production of prostaglandin (mostly PGE2) during the early phase of colitis.; The role of MO-derived NO in producing mucosal damage is still under active investigation. We inhibited MO-derived NO by decreasing its substrate arginine through the administration of bacterial-derived long-activity pegylated arginine deiminase (PEG-ADI). We showed decreased MO-derived NO production markedly dampens the severity of colitis in a mouse model.; IL-10 is the major anti-inflammatory cytokine produced by hepatic MO to counteract the effects of pro-inflammatory cytokines. We evaluated the kinetics of both IL-10 and pro-inflammatory cytokines during the process of liver inflammation. We show that IL-10 protects the liver against pro-inflammatory cytokines primarily by counteracting their pro-apoptotic effects.; SR-A is an important pattern recognition receptor on the surface of Kupffer cells that has been implicated in LPS clearance. We demonstrate in a defined mouse model that SR-A promotes ethanol-induced liver injury by increasing pro inflammatory cytokine expression and subsequent apoptosis. Subsequently, we showed that CD36 deficiency promoted the development of alcohol-induced hepatocellular injury by increasing the expression of both systemic pro-inflammatory cytokines and their liver mRNA. Furthermore, this led to accentuation of apoptosis.; Overall, this study identifies the role of different MSR and MO mediators in different models of inflammation. It may facilitate the further understanding of underlying pathophysiology in IBD and ALD.