Enhanced LPS-induced TNF alpha production in heat-shocked human promonocytic cells: regulation at the translational/post-translational level.
Heat shock proteins (hsps) play an important role in maintaining cellular homeostasis and protecting cells from various insults. Recent evidence also implicates hsps in the regulation of the immune response, particularly the inflammatory process. In the present study, we showed that human promonocytic cells (THP-1) produced elevated levels of tumor necrosis factor alpha (TNF alpha) after incubation with bacterial lipopolysaccharide (LPS) when cells were pre-stressed by a mild heat shock (HS) of 42 degrees C (1.5 h) followed by recovery at 37 degrees C (3 h) in comparison with non-stressed cells also stimulated with LPS. This enhanced TNF alpha production was not due to changes in nuclear factor-kappaB (NF-kappa B) activation, TNF alpha transcription rates, or mRNA stability. Thus, an effect at the translational or posttranslational level is likely responsible. Elevated production of TNF alpha was not observed when cells were stimulated with LPS immediately after stress or when HS temperature was increased to 43 degrees C. This negative effect of HS is likely due to a harmful effect of temperature. Moreover, enhanced LPS-induced TNF alpha production was not observed after differentiation of promonocytes into macrophage-like cells. Thus, our results show that the stress temperature, recovery period, and differentiation stage of the cell modulate the effect of HS on the inflammatory process.
Ferlito
Marcella
M
Division of Pediatric Surgery, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 746, Baltimore, MD 21205, USA.
De Maio
Antonio
A
D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006358:Hot Temperature; D006801:Humans; D007249:Inflammation; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013312:Stress, Physiological; D013696:Temperature; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016207:Cytokines; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin