Submitted to: Society for Leukocyte Biology Meetings Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 6/8/2007
Publication Date: 10/11/2007
Citation: Kogut, M.H., Genovese, K.J., He, H. 2007. Flagellin and lipopolysaccharide up-regulation of IL-6 and CXCLi2 gene expression in chicken heterophils is mediated by NF-kappaB and AP-1 pathways [abstract]. In: Proceedings of the Society for Leukocyte Biology, October 11-13, 2007, Cambridge, Massachusetts. p. 57.
Technical Abstract: The Toll-like receptor agonists, flagellin (FLG) and lipopolysaccharide (LPS) have been shown to stimulate chicken heterophils to induce the expression and secretion of pro-inflammatory cytokines by a mechanism involving the triggering of differential MEK-ERK signaling cascades. However, the translocation and activation of transcription factors potentially involved in the control of cytokine gene expression remains unknown. Herein, we examined the effects of FLG and LPS on the activation of the transcription factors NF-kappaB and AP-1 and their role in regulating heterophil activation leading to cytokine gene expression. Treatment of the heterophils with either FLG or LPS induced a significant increase in DNA binding by NF-kappaB family members p50, c-Rel, and RelB. Likewise, FLG and LPs induced a significant increase in DNA binding by the AP-1 family members c-Jun, JunD, and FosB. The activation of both NF-kappaB and AP-1 was inhibited following treatment of heterophils with specific inhibitors of NF-kappaB (Bay 11-7086), AP-1 (Tanshinone llA), ERK1/2 (U0126), and MEK (PD098059). Likewise, the up-regulation of gene expression of IL-6 and CXCLi2 were inhibited when the heterophils were treated with the specific inhibitors. Taken together these data demonstrate that although FLG (Rap1 to B-Raf to MEK to ERK) and LPS (Ras to Raf-1 to MEK to ERK) stimulate differential MEK-ERK signaling pathways, the up-regulation of expression of IL-6 and CXCLI2 was mediated by NF-kappaB and AP-1.