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

Julie K. Heimbach, Leonid L. Reznikov, Casey M. Calkins, Thomas N. Robinson, Charles A. Dinarello, Alden H. Harken, Xianzhong Meng

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Expression of heat shock proteins (HSP) is an adaptive response to cellular stress. Stress induces tumor necrosis factor (TNF)-α production. In turn, TNF-α induces HSP70 expression. However, osmotic stress or ultraviolet radiation activates TNF-α receptor I (TNFR-I) in the absence of TNF-α. We postulated that TNF-α receptors are involved in the induction of HSP70 by cellular stress. Peritoneal Mφ were isolated from wild-type (WT), TNF-α knockout (KO), and TNFR (I or II) KO mice. Cells were cultured overnight and then heat stressed at 43 ± 0.5°C for 30 min followed by a 4-h recovery at 37°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 Mφ, whereas TNFR-II KO Mφ exhibited HSP70 expression comparable to that in WT mice. Expression of HSP70 after heat stress in TNF-α KO Mφ was also similar to that in WT mice, suggesting that induction of HSP70 by TNFR-I occurs independently of TNF-α. In addition, levels of steady-state HSP70 mRNA were similar by RT-PCR in WT and TNFR-I KO Mφ 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 Mφ by a TNF-independent mechanism and support an intracellular role for TNFR-I.

Original languageEnglish (US)
Pages (from-to)C241-C247
JournalAmerican Journal of Physiology - Cell Physiology
Issue number1 50-1
StatePublished - 2001


  • Gene knockout
  • Reverse transcription-polymerase chain reaction
  • Splenocyte
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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