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

Papoutsopoulou, Stamatia ORCID: 0000-0001-6665-8508, Pollock, Liam, Williams, Jonathan M ORCID: 0000-0002-6617-0323, Abdul-Mahdi, Maya MLF ORCID: 0000-0003-1294-4693, Dobbash, Reyhaneh, Duckworth, Carrie A ORCID: 0000-0001-9992-7540 and Campbell, Barry J ORCID: 0000-0002-7407-012X (2022) Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo. Biology, 11 (10). 1377-.

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Official URL: http://dx.doi.org/10.3390/biology11101377

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 NFκB-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 NFκB pathway and its downstream targets in the small intestinal mucosa in vivo. We observed dysregulation of TNF, IκBα, 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 NFκB p65[RelA] activity, which was totally diminished in Il10-/- mice and correlated with reduced levels of TNF, IκBα, 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 NFκB signaling pathway axis in regulating intestinal mucosa homeostasis and response to inflammatory triggers in vivo.

Item Type:	Article
Uncontrolled Keywords:	NFκB, RelA, interleukin-10, intestine, mucosa, tumour necrosis factor
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	12 Dec 2022 09:49
Last Modified:	18 Jan 2023 19:40
DOI:	10.3390/biology11101377
Open Access URL:	https://www.mdpi.com/2079-7737/11/10/1377
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3166600