Interleukin-10 Deficiency Impacts on TNF-Induced NFκB 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 NFκB-driven transcriptional responses to TNF via an autocrine mechanism dependent on IL-10 secretion. Here...
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MDPI AG
2022-09-01
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| author | Stamatia Papoutsopoulou Liam Pollock Jonathan M. Williams Maya M. L. F. Abdul-Mahdi Reyhaneh Dobbash Carrie A. Duckworth Barry J. Campbell |
| author_facet | Stamatia Papoutsopoulou Liam Pollock Jonathan M. Williams Maya M. L. F. Abdul-Mahdi Reyhaneh Dobbash Carrie A. Duckworth Barry J. Campbell |
| author_sort | Stamatia Papoutsopoulou |
| collection | DOAJ |
| description | 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 <i>Il10<sup>−/−</sup></i> 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 <i>Il10<sup>−/−</sup></i> 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<i><sup>-</sup></i> 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 <i>Il10<sup>−/−</sup></i> 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. |
| first_indexed | 2024-03-09T20:40:49Z |
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| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T20:40:49Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | Biology |
| spelling | doaj.art-749ffbb3cb814308a477ad1c5c329e5c2023-11-23T22:58:35ZengMDPI AGBiology2079-77372022-09-011110137710.3390/biology11101377Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In VivoStamatia Papoutsopoulou0Liam Pollock1Jonathan M. Williams2Maya M. L. F. Abdul-Mahdi3Reyhaneh Dobbash4Carrie A. Duckworth5Barry J. Campbell6The Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UKThe Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UKPathobiology and Population Sciences, Royal Veterinary College, Hatfield AL9 7TA, UKThe Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UKThe Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UKThe Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UKThe Henry Wellcome Laboratories of Molecular & Cellular Gastroenterology, University of Liverpool, Liverpool L69 3GE, UKInterleukin-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 <i>Il10<sup>−/−</sup></i> 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 <i>Il10<sup>−/−</sup></i> 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<i><sup>-</sup></i> 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 <i>Il10<sup>−/−</sup></i> 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.https://www.mdpi.com/2079-7737/11/10/1377interleukin-10intestinemucosaNFκBRelAtumour necrosis factor |
| spellingShingle | Stamatia Papoutsopoulou Liam Pollock Jonathan M. Williams Maya M. L. F. Abdul-Mahdi Reyhaneh Dobbash Carrie A. Duckworth Barry J. Campbell Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo Biology interleukin-10 intestine mucosa NFκB RelA tumour necrosis factor |
| title | Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo |
| title_full | Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo |
| title_fullStr | Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo |
| title_full_unstemmed | Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo |
| title_short | Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo |
| title_sort | interleukin 10 deficiency impacts on tnf induced nfκb regulated responses in vivo |
| topic | interleukin-10 intestine mucosa NFκB RelA tumour necrosis factor |
| url | https://www.mdpi.com/2079-7737/11/10/1377 |
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