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

Radia Forteza, Yolanda Figueroa, Anastasia Mashukova, Vipin Dulam, Pedro J. Salas

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


The conserved proteins of the polarity complex made up of atypical PKC (aPKC, isoforms i 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 PKCi decreases NF-κB 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-κB 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-κB 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-κB.

Original languageEnglish (US)
Pages (from-to)2186-2197
Number of pages12
JournalMolecular biology of the cell
Issue number14
StatePublished - Jul 15 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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