Effect of the selective protein kinase C inhibitor, Ro-31-8220, on chemokine-induced Leukocyte recruitment in vivo

Abstract

The most critical and most important event in acute inflammation is the migration of neutrophils and other inflammatory cells from blood to the site of injury, immune response or infection. Leukocyte recruitment occurs in response to pro-inflammatory mediators such as cytokines and interleukins which are produced at the site of inflammation. Protein kinase C (PKC) is a family of kinases that are involved in the pathophysiology of a variety of inflammatory diseases or disorders such as arthritis, asthma and myocarditis. The effect of Ro-31-8220, the selective PKC inhibitor, on leukocyte transmigration in various inflammatory models is still incompletely understood. The present study explored the effect of the selective and pan inhibitor of PKC, Ro-31-8220, on CXCL1/KC induced leukocyte recruitment especially neutrophils in acute peritonitis model in mice. Ro-31-8220 treatment significantly attenuated the emigration of leukocytes predominately neutrophils in response to CXCL1/KC chemokine. Thereby, Ro-31-8220 treatment ameliorated CXCL1/KC induced acute peritonitis by interfering with emigration of leukocytes. Collectively, our study demonstrates that pharmacological inhibition of PKC in general, may provide the basic key of therapeutic strategy for many inflammatory diseases or immune linked disorders in which PKC was implicated