%0 Journal Article
%T Critical Role of Glycogen Synthase Kinase-3汕 in Regulating the Avian Heterophil Response to Salmonella enterica Serovar Enteritidis
%A Michael H. Kogut
%A Christina L. Swaggerty
%A Kenneth J. Genovese
%A Haiqi He
%A Huaijun Zhou
%A Ryan J. Arsenault
%J Frontiers in Veterinary Science
%D 2014
%R 10.3389/fvets.2014.00010
%X A microarray-assisted gene expression screen of chicken heterophils revealed glycogen synthase kinase-3汕 (GSK-3汕), a multifunctional Ser/Thr kinase, to be consistently upregulated 30每180 min following stimulation with Salmonella enterica serovar Enteritidis (S. Enteritidis). The present study was designed to delineate the role of GSK-3汕 in regulating the innate function of chicken heterophils in response to S. Enteritidis exposure. Using a specific GSK-3汕 ELISA assay, 30 min after infection with S. Enteritidis, heterophils had a significant decrease (p ≒ 0.05) in total GSK-3汕, but a significant increase (p ≒ 0.05) in phosphorylated GSK-3汕 (Ser9). By 60 min post-infection, there was no difference in the amount of phosphorylated GSK-3汕 (Ser9) in either the uninfected and infected heterophils. S. Enteritidis interaction with heterophils alters GSK-3汕 activity by stimulating phosphorylation at Ser9 and that peaks by 30 min post-infection. Further, inhibition of GSK3汕 with lithium chloride resulted in a significant decrease (p ≒ 0.05) in NF-百B activation and expression of IL-6, but induces a significant increase (p ≒ 0.05) in the expression of the anti-inflammatory cytokine, IL-10. Using a phospho-specific antibody array confirmed the phosphorylation of GSK-3汕 (Ser9) as well as the phosphorylation of the downstream cytokine-activated intracellular signaling pathway involved in stimulating immune responses, I百B, the I百B subunit IKK-汕, and the NF-百B subunits p105, p65, and c-Rel. Our data revealed that the phosphorylation of GSK-3汕 (Ser9) is responsible for inducing and controlling an innate response to the bacteria. Our findings suggest that the repression of GSK-3 activity is beneficial to the host cell and may act as a target for treatment in controlling intestinal colonization in chickens. Further experiments will define the in vivo modulation of GSK-3 as a potential alternative to antibiotics in salmonella and other intestinal bacterial infections.
%K glycogen synthase kinase-3ˋ
%K chickens
%K heterophils
%K Salmonella
%K innate immunity
%U http://www.frontiersin.org/Journal/10.3389/fvets.2014.00010/abstract