TRANSCRIPTIONAL INHIBITION OF ENDOTOXIN INDUCED MONOKINE SYNTHESIS FOLLOWING HEAT-SHOCK IN MURINE PERITONEAL-MACROPHAGES

被引:134
作者
SNYDER, YM [1 ]
GUTHRIE, L [1 ]
EVANS, GF [1 ]
ZUCKERMAN, SH [1 ]
机构
[1] ELI LILLY & CO,LILLY RES LAB,DEPT IMMUNOL,INDIANAPOLIS,IN 46285
关键词
INTERLEUKIN-1; TUMOR NECROSIS FACTOR; LIPOPOLYSACCHARIDES; ERYTHROPHAGOCYTOSIS;
D O I
10.1002/jlb.51.2.181
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The role of heat shock proteins (HSP) during the inflammatory response has been controversial. The effect of heat shock (HS) on the synthesis of the monokines tumor necrosis factor (TNF) and interleukin 1 (IL-1) by endotoxin-stimulated thioglycollate-elicited peritoneal macrophages was investigated. HS was deemed to have affected macrophages if a 70 kD HSP appeared on SDS gels; identity of this protein as the highly conserved HSP70 was then confirmed by immunoprecipitation. Maximal increases in HSP70 were apparent 2-5 h after HS at 45-degrees-C for 12 min. Synthesis of HSP70 was no longer detected 24 h post HS. A reciprocal relationship between HSP70 and TNF was apparent in kinetic studies. TNF was not detected in culture supernatants if macrophages were endotoxin-stimulated 2 to 6 h after HS; however, the same stimulation 24 h later induced significant TNF secretion. RNA analysis of HS and non-HS macrophage cultures demonstrated a 60-fold reduction in TNF message in the HS macrophages 1 h after endotoxin stimulation. TNF mRNA levels remained depressed at 6 h while the HSP70 message had increased 30-fold. The ability of HS macrophages to ingest antibody-coated erythrocytes was not significantly affected following heat treatment. Macrophage response to HS can be said to inhibit transcription of inducible monokines while retaining other macrophage functions.
引用
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页码:181 / 187
页数:7
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