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The p110α and p110β isoforms of class I phosphatidylinositol 3-kinase are involved in toll-like receptor 5 signaling in epithelial cells.


ABSTRACT: Bacterial flagellin triggers inflammation in mammalian cells via Toll-like receptor (TLR) 5. Release of the chemokine IL-8 in response to flagellin involves NF-κB, p38 MAP kinase, and phosphatidylinositol 3-kinase (PI3K). However, PI3K has been reported to be either pro- or anti-inflammatory in different model systems. We hypothesized that this could be due to different activities of the p110α and β isoforms of PI3K. PI3K and Akt were rapidly activated in Caco-2 colon carcinoma cells by flagellin. Using a plasmid-based shRNA delivery system and novel p110 isoform-specific inhibitors, we found that flagellin-induced IL-8 production was dependent on both p110α and p110β. However in the mouse, inhibition of p110β but not p110α reduced the increase of serum IL-6 levels induced by intraperitoneal injection of flagellin. These data demonstrate that the p110α and β isoforms of class IA PI3K are both required for the proinflammatory response to flagellin.

SUBMITTER: Ivison SM 

PROVIDER: S-EPMC2952946 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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The p110α and p110β isoforms of class I phosphatidylinositol 3-kinase are involved in toll-like receptor 5 signaling in epithelial cells.

Ivison Sabine M SM   Khan Mohammed A S MA   Graham Nicholas R NR   Shobab Leila A LA   Yao Yu Y   Kifayet Arnawaz A   Sly Laura M LM   Steiner Theodore S TS  

Mediators of inflammation 20101003


<h4>Background</h4>Bacterial flagellin triggers inflammation in mammalian cells via Toll-like receptor (TLR) 5. Release of the chemokine IL-8 in response to flagellin involves NF-κB, p38 MAP kinase, and phosphatidylinositol 3-kinase (PI3K). However, PI3K has been reported to be either pro- or anti-inflammatory in different model systems. We hypothesized that this could be due to different activities of the p110α and β isoforms of PI3K.<h4>Results</h4>PI3K and Akt were rapidly activated in Caco-2  ...[more]

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