TNF receptor I is required for induction of macrophage heat shock protein 70

Am J Physiol Cell Physiol. 2001 Jul;281(1):C241-7. doi: 10.1152/ajpcell.2001.281.1.C241.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Expression Regulation
  • HSP70 Heat-Shock Proteins / biosynthesis*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Hot Temperature
  • Immunoblotting
  • Macrophages / metabolism*
  • Mice
  • Mice, Knockout
  • RNA / metabolism
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Spleen / cytology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • HSP70 Heat-Shock Proteins
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • RNA