Down-regulation of IL-1 beta biosynthesis by inducers of the heat-shock response.
The effect of heat on IL-1 beta biosynthesis was investigated in both THP-1 cells, a myelomonocytic cell line which can be induced to make IL-1 alpha and beta, and human peripheral blood adherent monocytes (PBMC). Induction of THP-1 cells with LPS at 39 to 41 degrees C for 2 to 4 h resulted in the expected increased synthesis of the heat-shock proteins hsp 70 and hsp 90 but decreased synthesis of the IL-1 beta precursor protein, p35 (and its mRNA), compared with control cells at 37 degrees C. This appeared to be a direct effect on p35 synthesis rather than a block in LPS induction because heat also acted on preinduced cells. PBMC similarly incubated for 4 h with LPS required a temperature of 41 to 42 degrees C to induce hsp and show a decrease in p35 synthesis. Chemical inducers of the heat-shock response (heavy metals, sulphydryl reagents) were also effective inhibitors of IL-1 beta biosynthesis. A correlation was seen between the extent of IL-1 beta reduction and the level of hsp induction by chemical inducers in both THP-1 cells and PBMC which suggests that the two responses are linked. In addition, a gold salt currently used for therapy of chronic inflammation, auranofin, induced hsp and inhibited IL-1 beta biosynthesis, whereas a second salt, sodium aurothiomalate, did neither. These results support the hypothesis that elevated temperature is one of the physiologic signals for down-regulation of IL-1 beta biosynthesis through a mechanism related to the induction of hsp.
D000210:Acute-Phase Reaction / Q000209:etiology / Q000378:metabolism; D001310:Auranofin / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008670:Metals / Q000494:pharmacology; D008969:Molecular Sequence Data
D006360:Heat-Shock Proteins; D007375:Interleukin-1; D008670:Metals; D006052:Gold Sodium Thiomalate; D001310:Auranofin