Bacterial endotoxin lipopolysaccharide modulates synthesis of the 70 kDa heat stress protein family.
Murine bacillus Calmette-Guerin activated macrophages release several monokines when triggered by the bacterial endotoxin lipopolysaccharide (LPS); this has recently been reported to be strongly influenced by the sequence of hyperthermic and LPS treatments. In the work reported here, it was found that LPS treatment markedly modulated the rate of synthesis of proteins in the heat stress protein (HSP) 70 family in these macrophages. The rate of synthesis of the HSP 70 family was slightly reduced if the cells were incubated with LPS 4 h prior to heating at 43 degrees C for 1 h, but was greatly reduced as the triggering time approached the initiation of heating and was nearly completely abrogated if the LPS triggering immediately preceded or followed heating. Near-normal rates of HSP 70 synthesis occurred if the triggering was delayed until 1-2 h after the heating ended. The LPS-triggered release of tumour necrosis factor (TNF) was also reduced as the time of LPS addition approached the heating time, but this depressed release preceded the effects on HSP 70 synthesis and did not recover for up to 3 h after heating. The effects of LPS on HSP 70 synthesis also occurred in a murine monocytic cell line, PU5-1.8, which releases TNF in response to LPS, and in a murine fibroblast cell line, NIH/3T3. This indicates that these effects are not restricted to cells of monocyte or macrophage lineage. The nature of the transcriptional or translational mechanisms controlling these responses is unknown, but these data may contribute to the understanding of (1) the regulation of the HSP 70 family and (2) TNF processing in stressed cells.
Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
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Tomasovic
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Klostergaard
D000818:Animals; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha