Interleukin-10 Deficiency Impacts on TNF-Induced NF kappa B Regulated Responses In Vivo

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 NF kappa B-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 NF kappa B pathway and its downstream targets in the small intestinal mucosa in vivo. We observed dysregulation of TNF, I kappa B alpha, 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 NF kappa B p65[RelA] activity, which was totally diminished in Il10(-/-) mice and correlated with reduced levels of TNF, I kappa B alpha, 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 naive, as well as TNF-injected Il10(-/-) mice. These data further support the importance of the IL-10-canonical NF kappa B signaling pathway axis in regulating intestinal mucosa homeostasis and response to inflammatory triggers in vivo.