Enhanced LPS-induced TNFα 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 (TNFα) after incubation with bacterial lipopolysaccharide (LPS) when cells were pre-stressed by a mild heat shock (HS) of 42°C (1.5 h) followed by recovery at 37°C (3 h) in comparison with non-stressed cells also stimulated with LPS. This enhanced TNFα production was not due to changes in nuclear factor-κB (NF-κB) activation, TNFα transcription rates, or mRNA stability. Thus, an effect at the translational or posttranslational level is likely responsible. Elevated production of TNFα was not observed when cells were stimulated with LPS immediately after stress or when HS temperature was increased to 43°C. This negative effect of HS is likely due to a harmful effect of temperature. Moreover, enhanced LPS-induced TNFα 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.