Presentation Title

Conditional Knockout of Polarity Complex (Atypical) aPKC Reveals an Anti-inflammatory Function Mediated by NF-κB

Speaker Credentials

Assistant Professor

Speaker Credentials

Ph.D.

College

College of Medical Sciences, MBS

Location

Nova Southeastern University, Davie, Florida, USA

Format

Poster

Start Date

16-2-2018 12:15 PM

End Date

16-2-2018 1:15 PM

Abstract

Objective. This study was conducted to investigate anti-inflammatory role of atypical PKC (aPKC) in the intestinal epithelium. Background. Inflammatory Bowel Disease (IBD) is a complex multi-causal condition arising from a combination of genetic predisposition and environmental challenges by intestinal bacteria. The intestinal epithelium constitutes the essential barrier against the potentially damaging factors and agents which exist in the gut lumen. It has been established that in IBD multiple proinflammatory cytokines, including TNF alpha, signal on the intestinal epithelium causing activation of the innate immunity pathways such as NF-kB. In turn, these pathways cause disassembly of the tight junctions and permeabilization of the intestinal barrier resulting in persistent inflammation. Our interest in the possible role of aPKC in inflammatory pathways was sparked when we observed that aPKC was deeply down-regulated in intestinal epithelia in samples from IBD patients. Methods. We used aPKC flox/flox mouse to obtain a conditional knockout in intestinal epithelia. We were able to achieve full aPKC down-regulation in small intestine villi and colon surface epithelium. Results. The results show that aPKC is dispensable for polarity after cell differentiation. At the same time aPKC defect resulted in increased NF-κB activity and elevated expression of proinflammatory cytokines. In contrast, expression of anti-inflammatory IL-10 decreased. Conclusion. We conclude that epithelial aPKC acts upstream of multiple mechanisms that participate in the inflammatory response in the intestine, including, but not restricted to, NF-κB. Grants. This study was partially funded by a President's Faculty Research and Development Grant to A. Mashukova.

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Feb 16th, 12:15 PM Feb 16th, 1:15 PM

Conditional Knockout of Polarity Complex (Atypical) aPKC Reveals an Anti-inflammatory Function Mediated by NF-κB

Nova Southeastern University, Davie, Florida, USA

Objective. This study was conducted to investigate anti-inflammatory role of atypical PKC (aPKC) in the intestinal epithelium. Background. Inflammatory Bowel Disease (IBD) is a complex multi-causal condition arising from a combination of genetic predisposition and environmental challenges by intestinal bacteria. The intestinal epithelium constitutes the essential barrier against the potentially damaging factors and agents which exist in the gut lumen. It has been established that in IBD multiple proinflammatory cytokines, including TNF alpha, signal on the intestinal epithelium causing activation of the innate immunity pathways such as NF-kB. In turn, these pathways cause disassembly of the tight junctions and permeabilization of the intestinal barrier resulting in persistent inflammation. Our interest in the possible role of aPKC in inflammatory pathways was sparked when we observed that aPKC was deeply down-regulated in intestinal epithelia in samples from IBD patients. Methods. We used aPKC flox/flox mouse to obtain a conditional knockout in intestinal epithelia. We were able to achieve full aPKC down-regulation in small intestine villi and colon surface epithelium. Results. The results show that aPKC is dispensable for polarity after cell differentiation. At the same time aPKC defect resulted in increased NF-κB activity and elevated expression of proinflammatory cytokines. In contrast, expression of anti-inflammatory IL-10 decreased. Conclusion. We conclude that epithelial aPKC acts upstream of multiple mechanisms that participate in the inflammatory response in the intestine, including, but not restricted to, NF-κB. Grants. This study was partially funded by a President's Faculty Research and Development Grant to A. Mashukova.