Effects of cytokines on rat insulinoma INS-1 cells.
To investigate further the role of cytokines in the pathogenesis of type I insulin-dependent diabetes mellitus, the effects of interleukin-1 beta (IL-1), tumour necrosis factor-alpha (TNF) and gamma-interferon (IFN) were tested on rat insulinoma INS-1 cells. Whereas TNF and IFN had, respectively, a minor or no effect on insulin production, IL-1 caused a time- and dose-dependent decrease in insulin release and lowered the insulin content as well as the preproinsulin mRNA content of INS-1 cells. Both IL-1 and TNF exerted a cytostatic effect, estimated by a decrease in [3H]thymidine incorporation, while only IL-1 decreased cell viability as measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. The glutathione content of INS-1 cells was shown to be modulated by the presence of 2-mercaptoethanol in the culture medium, but was not affected by IL-1 or TNF. In conclusion, INS-1 cell culture is considered to be a useful model for studying the effect of cytokines on insulin-producing cells. The differentiated features of these cells will permit several questions to be addressed regarding the mechanism of action of IL-1 and eventually other cytokines, both at the level of gene expression and of intracellular signalling.
Janjic
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Laboratoires de recherche Louis Jeantet, Centre Médical Universitaire, University of Geneva, Switzerland.
Asfari
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M
D000818:Animals; D015152:Blotting, Northern; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis*; D007340:Insulinoma / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D011384:Proinsulin / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007328:Insulin; D007375:Interleukin-1; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; C013737:preproinsulin; D007371:Interferon-gamma; D011384:Proinsulin; D005978:Glutathione