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

Papoutsopoulou, Stamatia; Pollock, Liam; Williams, Jonathan M.; Abdul-Mahdi, Maya M. L. F.; Dobbash, Reyhaneh; Duckworth, Carrie A.; Campbell, Barry J.


Stamatia Papoutsopoulou

Liam Pollock

Jonathan M. Williams

Maya M. L. F. Abdul-Mahdi

Reyhaneh Dobbash

Carrie A. Duckworth

Barry J. Campbell


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.


Papoutsopoulou, S., Pollock, L., Williams, J. M., Abdul-Mahdi, M. M. L. F., Dobbash, R., Duckworth, C. A., & Campbell, B. J. (in press). Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo. Biology, 11(10), 1377.

Journal Article Type Article
Acceptance Date Sep 17, 2022
Online Publication Date Sep 20, 2022
Deposit Date Aug 25, 2023
Publicly Available Date Aug 25, 2023
Journal Biology
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 11
Issue 10
Pages 1377
Keywords General Agricultural and Biological Sciences; General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology


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