Interleukin-1 induction of tumor necrosis factor-alpha mRNA and bioactive tumor necrosis factor-alpha in a pancreatic beta-cell line by a mechanism requiring no de novo protein synthesis.
Interleukin-1 (IL-1) has been implicated as an effector in insulitis of Type 1 (insulin-dependent) diabetes. Exposure of a beta-cell line (beta TC1) to IL-1 beta resulted in an increase of preproinsulin mRNA at 0.5 h followed by a gradual decrease. Tumor necrosis factor-alpha (TNF-alpha) mRNA expression by beta TC1 cells was demonstrated 1-3 h after the addition of IL-1 beta. TNF bioactivity was detected in homogenates of beta TC1 cells exposed to IL-1. The supplementation of cycloheximide (CHX) together with IL-1 beta resulted in the superinduction of TNF-alpha mRNA, suggesting that de novo protein synthesis is not required in IL-1-induced TNF-alpha mRNA expression. Endogenous TNF-alpha of beta-cells may be involved in the islet lesion of type 1 diabetes.
Takane
N
N
Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Yamada
K
K
Otabe
S
S
Inoue
M
M
Nonaka
K
K
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007328:Insulin; D007376:Interleukin-2 / Q000494:pharmacology*; D007515:Islets of Langerhans; D007700:Kinetics; D051379:Mice; D011384:Proinsulin / Q000096:biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000199:Actins; D007328:Insulin; D007376:Interleukin-2; D011498:Protein Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C013737:preproinsulin; D011384:Proinsulin; D003513:Cycloheximide