Journal
BIOLOGY-BASEL
Volume 11, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/biology11101377
Keywords
interleukin-10; intestine; mucosa; NF kappa B; RelA; tumour necrosis factor
Categories
Funding
- Wellcome Trust through the 4-year PhD programme in Molecular and Cellular Physiology, at the University of Liverpool [102172/B/13/Z]
- Medical Research Council, UK [MR/P023606/1]
- Wellcome Trust [102172/B/13/Z] Funding Source: Wellcome Trust
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IL-10 plays a crucial role in protecting against intestinal inflammation by regulating the NF kappa B pathway. Deficiency of IL-10 leads to dysregulation of gene and protein expression related to inflammation in the small intestine, as well as disrupted levels of IgA in serum and intestinal mucosa.
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.
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