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: GH inhibits interferon-gamma-induced signal transducer and activator of transcription-1 activation and expression of the inducible isoform of nitric oxide synthase in INS-1 cells.
    Author: Sekine N, Fukumoto S, Ishikawa T, Okazaki T, Fujita T.
    Journal: Endocrinology; 2001 Sep; 142(9):3909-16. PubMed ID: 11517169.
    Abstract:
    Interferon-gamma and TNFalpha synergistically induce the inducible isoform of nitric oxide synthase and elicit severe cytotoxicity in pancreatic beta-cells. We demonstrate here that GH, the well known beta-cell mitogen, inhibits nitric oxide production by reducing inducible nitric oxide synthase gene induction by the two cytokines and counteracts their cytotoxic effect in insulin-secreting INS-1 cells. To elucidate the underlying mechanism, we examined activation of the transcription factors implicated in the induction of inducible nitric oxide synthase, signal transducer and activator of transcription-1, and nuclear factor-kappa B. GH inhibited tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription-1 promoted by interferon-gamma, whereas nuclear factor-kappa B activation by TNFalpha was not affected by GH. GH was found to induce suppressor of cytokine signaling-1 and -3, both of which are able to inhibit interferon-gamma activation of signal transducer and activator of transcription-1, suggesting that they are likely to mediate the inhibitory action of GH. Finally, exposure of INS-1 cells to interferon-gamma resulted in the impairment of insulin secretion in response to glucose, which was restored by the addition of GH. These results indicate that GH counteracts the effect of interferon-gamma through the inhibition of signal transducer and activator of transcription-1. This action of GH may be sufficient to suppress the synergistic induction of inducible nitric oxide synthase by interferon-gamma and TNFalpha, thereby preventing the cytotoxicity to beta-cells.
    [Abstract] [Full Text] [Related] [New Search]