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Conditional knockout of polarity complex (atypical) PKC? reveals an anti-inflammatory function mediated by NF-?B.

ABSTRACT: The conserved proteins of the polarity complex made up of atypical PKC (aPKC, isoforms ? and ?), Par6, and Par3 determine asymmetry in several cell types, from Caenorhabditis elegans oocytes to vertebrate epithelia and neurons. We previously showed that aPKC is down-regulated in intestinal epithelia under inflammatory stimulation. Further, expression of constitutively active PKC? decreases NF-?B activity in an epithelial cell line, the opposite of the effect reported in other cells. Here we tested the hypothesis that aPKC has a dual function in epithelia, inhibiting the NF-?B pathway in addition to having a role in apicobasal polarity. We achieved full aPKC down-regulation in small intestine villi and colon surface epithelium using a conditional epithelium-specific knockout mouse. The results show that aPKC is dispensable for polarity after cell differentiation, except for known targets, including ROCK and ezrin, claudin-4 expression, and barrier permeability. The aPKC defect resulted in increased NF-?B activity, which could be rescued by IKK and ROCK inhibitors. It also increased expression of proinflammatory cytokines. In contrast, expression of anti-inflammatory IL-10 decreased. 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-?B.

SUBMITTER: Forteza R

PROVIDER: S-EPMC4945138 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Conditional knockout of polarity complex (atypical) PKCι reveals an anti-inflammatory function mediated by NF-κB.

Forteza Radia R Figueroa Yolanda Y Mashukova Anastasia A Dulam Vipin V Salas Pedro J PJ

Molecular biology of the cell 20160525 14

The conserved proteins of the polarity complex made up of atypical PKC (aPKC, isoforms ι and ζ), Par6, and Par3 determine asymmetry in several cell types, from Caenorhabditis elegans oocytes to vertebrate epithelia and neurons. We previously showed that aPKC is down-regulated in intestinal epithelia under inflammatory stimulation. Further, expression of constitutively active PKCι decreases NF-κB activity in an epithelial cell line, the opposite of the effect reported in other cells. Here we test ...[more]

PMID: 27226486

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Dataset Information

Conditional knockout of polarity complex (atypical) PKC? reveals an anti-inflammatory function mediated by NF-?B.

Publications

Conditional knockout of polarity complex (atypical) PKCι reveals an anti-inflammatory function mediated by NF-κB.

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