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Down-regulation of IL-1 beta biosynthesis by inducers of the heat-shock response.

J A Schmidt and E Abdulla
J Immunol September 15, 1988, 141 (6) 2027-2034;
J A Schmidt
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E Abdulla
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Abstract

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.

  • Copyright © 1988 by American Association of Immunologists

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The Journal of Immunology
Vol. 141, Issue 6
15 Sep 1988
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Down-regulation of IL-1 beta biosynthesis by inducers of the heat-shock response.
J A Schmidt, E Abdulla
The Journal of Immunology September 15, 1988, 141 (6) 2027-2034;

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Down-regulation of IL-1 beta biosynthesis by inducers of the heat-shock response.
J A Schmidt, E Abdulla
The Journal of Immunology September 15, 1988, 141 (6) 2027-2034;
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Print ISSN 0022-1767        Online ISSN 1550-6606