Endogenous tumor necrosis factor-alpha production by a pancreatic beta-cell line: inhibitory effects of hydrocortisone and nicotinamide.
The purpose of this study was to examine regulation of interleukin-1(IL-1)-induced tumor necrosis factor-alpha (TNF-alpha) production by a mouse beta-cell line (beta TC1). Three-hour incubation of beta TC1 cells with 5 U/ml of IL-1 beta results in the expression of TNF-alpha mRNA and intracellular accumulation of TNF-alpha. It has been shown that glucocorticoids and immunosuppressive agents such as cyclosporin and FK-506 inhibit TNF-alpha generation by T-lymphocytes and monocytes. Hydrocortisone of 1 and 10 mumol/l suppressed TNF-alpha mRNA levels and the TNF-alpha content of beta TC1 cells exposed to IL-1 beta, whereas neither cyclosporin nor FK-506 altered the TNF-alpha content. Nicotinamide of 5-10 mmol/l also reduced TNF-alpha mRNA and TNF-alpha protein levels in beta TC1 cells. Addition of exogenous TNF-alpha did not inhibit IL-1-induced transcription of TNF-alpha gene. These observations support the potential therapeutic role of glucocorticoids and nicotinamide in protecting beta-cells against cytokine-mediated damage, although glucocorticoid agonists have hyperglycemic metabolic effects.
Yamada
K
K
Department of Medicine, Kurume University School of Medicine, Japan. yamada@kurume.ktarn.or.jp
Takane-Gyotoku
N
N
Inada
C
C
Nonaka
K
K
D000818:Animals; D002460:Cell Line; D006854:Hydrocortisone / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009536:Niacinamide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D006854:Hydrocortisone