TNF receptor I is required for induction of macrophage heat shock protein 70. Am J Physiol Cell Physiol 2001 Jul;281(1):C241-7
Date
06/13/2001Pubmed ID
11401847DOI
10.1152/ajpcell.2001.281.1.C241Scopus ID
2-s2.0-0034816776 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Expression of heat shock proteins (HSP) is an adaptive response to cellular stress. Stress induces tumor necrosis factor (TNF)-alpha production. In turn, TNF-alpha induces HSP70 expression. However, osmotic stress or ultraviolet radiation activates TNF-alpha receptor I (TNFR-I) in the absence of TNF-alpha. We postulated that TNF-alpha receptors are involved in the induction of HSP70 by cellular stress. Peritoneal Mphi were isolated from wild-type (WT), TNF-alpha knockout (KO), and TNFR (I or II) KO mice. Cells were cultured overnight and then heat stressed at 43 +/- 0.5 degrees C for 30 min followed by a 4-h recovery at 37 degrees C. Cellular HSP70 expression was induced by heat stress or exposure to endotoxin [lipopolysaccharide (LPS)] as determined by immunoblotting. HSP70 expression induced by either heat or LPS was markedly decreased in TNFR-I KO Mphi, whereas TNFR-II KO Mphi exhibited HSP70 expression comparable to that in WT mice. Expression of HSP70 after heat stress in TNF-alpha KO Mphi was also similar to that in WT mice, suggesting that induction of HSP70 by TNFR-I occurs independently of TNF-alpha. In addition, levels of steady-state HSP70 mRNA were similar by RT-PCR in WT and TNFR-I KO Mphi despite differences in protein expression. Furthermore, the effect of TNFR-I appears to be cell specific, since HSP70 expression in splenocytes isolated from TNFR-I KO was similar to that in WT splenocytes. These studies demonstrate that TNFR-I is required for the synthesis of HSP70 in stressed Mphi by a TNF-independent mechanism and support an intracellular role for TNFR-I.
Author List
Heimbach JK, Reznikov LL, Calkins CM, Robinson TN, Dinarello CA, Harken AH, Meng XAuthor
Casey Matthew Calkins MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCells, Cultured
Gene Expression Regulation
HSP70 Heat-Shock Proteins
Hot Temperature
Immunoblotting
Macrophages
Mice
Mice, Knockout
RNA
Receptors, Tumor Necrosis Factor
Spleen
Tumor Necrosis Factor-alpha