G-Protein-Coupled Receptor Kinase-5 Mediates Inflammation but Does Not Regulate Cellular Infiltration or Bacterial Load in a Polymicrobial Sepsis Model in Mice

• DOI: 10.1159/000347002
• Publication Date: 2013-03-13T07:42:09Z
• Authors: Nandakumar Packir...; Taehyung Lee; Pongali B. Raghav...; Haritha Durairaj; Hongbing Wang; Narayanan Parames...
• Keywords: Pathogenesis

NFκB-dependent signaling is an important modulator of inflammation in several diseases including sepsis. G-protein-coupled receptor kinase-5 (GRK5) evolutionarily conserved regulator the NFκB pathway. We hypothesized that GRK5 via regulation plays role pathogenesis To test this we utilized a clinically relevant polymicrobial sepsis model mice were deficient GRK5. subjected wild-type (WT) and knockout (KO) to cecal ligation puncture (CLP)-induced assessed various events pathogenesis. CLP induced significant inflammatory response WT was markedly attenuated KO mice. determine mechanisms activation sepsis-induced inflammation, levels IκBa phosphorylation expression genes liver two genotypes. Both gene significantly inhibited compared Interestingly, however, did not modulate either immune cell infiltration (to primary site infection) or local/systemic bacterial load subsequent induction. In contrast deficiency plasma corticosterone consequent thymocyte apoptosis vivo. Associated with these outcomes, CLP-induced mortality prevented presence antibiotics. Together, our studies demonstrate thymic implicate as potential molecular target