Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo

Abstract

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has a major protective role against intestinal inflammation. We recently revealed that intestinal epithelial cells in vitro regulate NFkB-driven transcriptional responses to TNF via an autocrine mechanism dependent on IL-10 secretion. Here in this study, we investigated the impact of IL-10 deficiency on the NFkB pathway and its downstream targets in the small intestinal mucosa in vivo. We observed dysregulation of TNF, IkBa, and A20 gene and protein expression in the small intestine of steady-state or TNF-injected Il10-/- mice, compared to wild-type C57BL6/J counterparts. Upon TNF injection, tissue from the small intestine showed upregulation of NFkB p65[RelA] activity, which was totally diminished in Il10-/- mice and correlated with reduced levels of TNF, IkBa, and A20 expression. In serum, whilst IgA levels were noted to be markedly downregulated in IL-10-deficient- mice, normal levels of mucosal IgA were seen in intestine mucosa. Importantly, dysregulated cytokine/chemokine levels were observed in both serum and intestinal tissue lysates from naïve, as well as TNF-injected Il10-/- mice. These data further support the importance of the IL-10-canonical NFkB signaling pathway axis in regulating intestinal mucosa homeostasis and response to inflammatory triggers in vivo.

Macrophage modulation in activation process induced immune thrombocytopenia

“…(61) The antiinflammatory cytokine IL10 exerts its effects by blocking the synthesis of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF) in monocytes/macrophages. (62)(63)(64)(65)…”