| First Author | Forteza R | Year | 2016 |
| Journal | Mol Biol Cell | Volume | 27 |
| Issue | 14 | Pages | 2186-97 |
| PubMed ID | 27226486 | Mgi Jnum | J:278595 |
| Mgi Id | MGI:6359191 | Doi | 10.1091/mbc.E16-02-0086 |
| Citation | Forteza R, et al. (2016) Conditional knockout of polarity complex (atypical) PKCiota reveals an anti-inflammatory function mediated by NF-kappaB. Mol Biol Cell 27(14):2186-97 |
| abstractText | The conserved proteins of the polarity complex made up of atypical PKC (aPKC, isoforms iota and zeta), 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 PKCiota decreases NF-kappaB 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-kappaB 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-kappaB 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-kappaB. |
