These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Activation of phosphatidylinositol 3-kinase by interleukin-13. An inhibitory signal for inducible nitric-oxide synthase expression in epithelial cell line HT-29.
    Author: Wright K, Ward SG, Kolios G, Westwick J.
    Journal: J Biol Chem; 1997 May 09; 272(19):12626-33. PubMed ID: 9139718.
    Abstract:
    The human colonic epithelial cell line HT-29 can be induced by a combination of the cytokines interleukin (IL)-1alpha, tumor necrosis factor alpha, and interferon-gamma to express the inducible form of nitric-oxide synthase (iNOS; Kolios, G., Brown, Z., Robson, R., Robertson, D. A. F., & Westwick, J. (1995) Br. J. Pharmacol. 116, 2866-2872). IL-13 is a potent inhibitor of cytokine-induced iNOS mRNA expression and nitric oxide generation in HT-29 cells via an unknown mechanism. We report here that in HT-29 cells, IL-13 induces a concentration and time-dependent increase in the formation of the lipid products of phosphatidylinositol (PtdIns) 3-kinase, namely phosphatidylinositol (3,4)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate. IL-13 also induces a parallel concentration and time-dependent increase in the in vitro lipid kinase activity present in immunoprecipitates of the p85 regulatory subunit of PtdIns 3-kinase. In addition, we also demonstrate that IL-13 stimulates the tyrosine phosphorylation of the adaptor molecule insulin receptor substrate 1, which may facilitate receptor coupling to PtdIns 3-kinase. Both the increases in D-3 phosphatidylinositol lipids and the increased in vitro lipid kinase activity of p85 immunoprecipitates were inhibited by wortmannin and LY294002. Inhibition of the PtdIns 3-kinase activity was paralleled by a reversal of the ability of IL-13 to inhibit iNOS mRNA expression and nitrite generation in HT-29 cells. These data demonstrate that the activation of PtdIns 3-kinase by IL-13 is a key signal that is responsible for the inhibition of iNOS transcription in activated epithelial cells.
    [Abstract] [Full Text] [Related] [New Search]