STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production. / Jensen, Janne; Galsgaard, Elisabeth D; Karlsen, Allan E; Lee, Ying C; Nielsen, Jens H.

I: Journal of Endocrinology, Bind 187, Nr. 1, 2005, s. 25-36.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Jensen, J, Galsgaard, ED, Karlsen, AE, Lee, YC & Nielsen, JH 2005, 'STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production.', Journal of Endocrinology, bind 187, nr. 1, s. 25-36. https://doi.org/10.1677/joe.1.06086

APA

Jensen, J., Galsgaard, E. D., Karlsen, A. E., Lee, Y. C., & Nielsen, J. H. (2005). STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production. Journal of Endocrinology, 187(1), 25-36. https://doi.org/10.1677/joe.1.06086

Vancouver

Jensen J, Galsgaard ED, Karlsen AE, Lee YC, Nielsen JH. STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production. Journal of Endocrinology. 2005;187(1):25-36. https://doi.org/10.1677/joe.1.06086

Author

Jensen, Janne ; Galsgaard, Elisabeth D ; Karlsen, Allan E ; Lee, Ying C ; Nielsen, Jens H. / STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production. I: Journal of Endocrinology. 2005 ; Bind 187, Nr. 1. s. 25-36.

Bibtex

@article{14069160acd111ddb538000ea68e967b,
title = "STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production.",
abstract = "The proinflammatory cytokines interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are toxic to pancreatic beta-cells and are implicated in the pathogenesis of type 1 diabetes. We have previously found that GH and prolactin (PRL) stimulate both proliferation and insulin production in pancreatic beta-cells and rat insulin-producing INS-1 cells. Here we report that human (h) GH can prevent the apoptotic effects of IL-1beta, IFN-gamma and TNF-alpha in INS-1 and INS-1E cells. Using adenovirus-mediated gene transfer, we found that the anti-apoptotic effect of hGH is abrogated by expression of a dominant negative signal transducer and activator of transcription (STAT5) mutant in INS-1E cells. hGH and the cytotoxic cytokines was found to additively increase suppressor of cytokine signalling-3 mRNA expression after 4 h of exposure. In order to identify possible targets for the STAT5-mediated protection of INS-1E cells, we studied the effect of hGH on activation of the transcription factors STAT1 and nuclear factor-kappaB (NF-kappaB) by IFN-gamma and IL-1beta+TNF-alpha respectively. Gel retardation experiments showed that hGH affects neither IFN-gamma+TNF-alpha-induced STAT1 DNA binding nor IL-1beta and IFN-gamma+TNF-alpha-induced NFkappaB DNA binding. The lack of influence of hGH on cytokine-mediated activation of STAT1 and NFkappaB is in accordance with the finding that hGH had only a minor effect on cytokine-induced inducible nitric oxide synthase (iNOS) gene expression and in fact augmented the IL-1beta-stimulated nitric oxide production. As the anti-apoptotic Bcl-xL gene has been shown to harbour a STAT5-binding element we measured the expression of Bcl-xL as well as the pro-apoptotic Bax. We found that hGH increased the Bcl-xL/Bax ratio both in the absence and in the presence of cytotoxic cytokines. In conclusion, these results suggested that GH and PRL protect beta-cells against cytotoxic cytokines via STAT5-dependent mechanisms distal to iNOS activation possibly at the level of Bcl-xL.",
author = "Janne Jensen and Galsgaard, {Elisabeth D} and Karlsen, {Allan E} and Lee, {Ying C} and Nielsen, {Jens H}",
note = "Keywords: Animals; Apoptosis; Blotting, Western; Human Growth Hormone; Humans; In Situ Nick-End Labeling; Insulin; Interferon Type II; Interleukin-1; Islets of Langerhans; Mice; Nitric Oxide; Rats; Reverse Transcriptase Polymerase Chain Reaction; STAT5 Transcription Factor; Tumor Necrosis Factor-alpha",
year = "2005",
doi = "10.1677/joe.1.06086",
language = "English",
volume = "187",
pages = "25--36",
journal = "Journal of Endocrinology",
issn = "0022-0795",
publisher = "BioScientifica Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production.

AU - Jensen, Janne

AU - Galsgaard, Elisabeth D

AU - Karlsen, Allan E

AU - Lee, Ying C

AU - Nielsen, Jens H

N1 - Keywords: Animals; Apoptosis; Blotting, Western; Human Growth Hormone; Humans; In Situ Nick-End Labeling; Insulin; Interferon Type II; Interleukin-1; Islets of Langerhans; Mice; Nitric Oxide; Rats; Reverse Transcriptase Polymerase Chain Reaction; STAT5 Transcription Factor; Tumor Necrosis Factor-alpha

PY - 2005

Y1 - 2005

N2 - The proinflammatory cytokines interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are toxic to pancreatic beta-cells and are implicated in the pathogenesis of type 1 diabetes. We have previously found that GH and prolactin (PRL) stimulate both proliferation and insulin production in pancreatic beta-cells and rat insulin-producing INS-1 cells. Here we report that human (h) GH can prevent the apoptotic effects of IL-1beta, IFN-gamma and TNF-alpha in INS-1 and INS-1E cells. Using adenovirus-mediated gene transfer, we found that the anti-apoptotic effect of hGH is abrogated by expression of a dominant negative signal transducer and activator of transcription (STAT5) mutant in INS-1E cells. hGH and the cytotoxic cytokines was found to additively increase suppressor of cytokine signalling-3 mRNA expression after 4 h of exposure. In order to identify possible targets for the STAT5-mediated protection of INS-1E cells, we studied the effect of hGH on activation of the transcription factors STAT1 and nuclear factor-kappaB (NF-kappaB) by IFN-gamma and IL-1beta+TNF-alpha respectively. Gel retardation experiments showed that hGH affects neither IFN-gamma+TNF-alpha-induced STAT1 DNA binding nor IL-1beta and IFN-gamma+TNF-alpha-induced NFkappaB DNA binding. The lack of influence of hGH on cytokine-mediated activation of STAT1 and NFkappaB is in accordance with the finding that hGH had only a minor effect on cytokine-induced inducible nitric oxide synthase (iNOS) gene expression and in fact augmented the IL-1beta-stimulated nitric oxide production. As the anti-apoptotic Bcl-xL gene has been shown to harbour a STAT5-binding element we measured the expression of Bcl-xL as well as the pro-apoptotic Bax. We found that hGH increased the Bcl-xL/Bax ratio both in the absence and in the presence of cytotoxic cytokines. In conclusion, these results suggested that GH and PRL protect beta-cells against cytotoxic cytokines via STAT5-dependent mechanisms distal to iNOS activation possibly at the level of Bcl-xL.

AB - The proinflammatory cytokines interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are toxic to pancreatic beta-cells and are implicated in the pathogenesis of type 1 diabetes. We have previously found that GH and prolactin (PRL) stimulate both proliferation and insulin production in pancreatic beta-cells and rat insulin-producing INS-1 cells. Here we report that human (h) GH can prevent the apoptotic effects of IL-1beta, IFN-gamma and TNF-alpha in INS-1 and INS-1E cells. Using adenovirus-mediated gene transfer, we found that the anti-apoptotic effect of hGH is abrogated by expression of a dominant negative signal transducer and activator of transcription (STAT5) mutant in INS-1E cells. hGH and the cytotoxic cytokines was found to additively increase suppressor of cytokine signalling-3 mRNA expression after 4 h of exposure. In order to identify possible targets for the STAT5-mediated protection of INS-1E cells, we studied the effect of hGH on activation of the transcription factors STAT1 and nuclear factor-kappaB (NF-kappaB) by IFN-gamma and IL-1beta+TNF-alpha respectively. Gel retardation experiments showed that hGH affects neither IFN-gamma+TNF-alpha-induced STAT1 DNA binding nor IL-1beta and IFN-gamma+TNF-alpha-induced NFkappaB DNA binding. The lack of influence of hGH on cytokine-mediated activation of STAT1 and NFkappaB is in accordance with the finding that hGH had only a minor effect on cytokine-induced inducible nitric oxide synthase (iNOS) gene expression and in fact augmented the IL-1beta-stimulated nitric oxide production. As the anti-apoptotic Bcl-xL gene has been shown to harbour a STAT5-binding element we measured the expression of Bcl-xL as well as the pro-apoptotic Bax. We found that hGH increased the Bcl-xL/Bax ratio both in the absence and in the presence of cytotoxic cytokines. In conclusion, these results suggested that GH and PRL protect beta-cells against cytotoxic cytokines via STAT5-dependent mechanisms distal to iNOS activation possibly at the level of Bcl-xL.

U2 - 10.1677/joe.1.06086

DO - 10.1677/joe.1.06086

M3 - Journal article

C2 - 16214938

VL - 187

SP - 25

EP - 36

JO - Journal of Endocrinology

JF - Journal of Endocrinology

SN - 0022-0795

IS - 1

ER -

ID: 8465514