The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in Toll-Like Receptor 5 Signaling in Epithelial Cells. (25th July 2010)

• Record Type: Journal Article
• Authors: Ivison, Sabine M.; Khan, Mohammed A. S.; Graham, Nicholas R.; Shobab, Leila A.; Yao, Yu; Kifayet, Arnawaz; Sly, Laura M.; Steiner, Theodore S.
• Other Names: Parker Andrew Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2010(2010)
• Publication Date: 2010-07-25
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2010/652098
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Background . 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-κ B, 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 andβ isoforms of PI3K. Results . 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. Conclusions . These data demonstrate that the p110α andβ isoforms of class IA PI3K are both required for the proinflammatory response to flagellin.