Acquisition mechanism of heme oxygenase-1 induction by heat shock in human monocytic cell line THP-1 after differentiation to macrophage-like cells.

Heme oxygenase-1 (HO-1) is unique to be directly regulated by diverse stress-responsible transcription factors, however, the cross-talk between oxidative stress and heat shock stress has not been completely elucidated. It is widely accepted that HO activity is not induced by heat shock in cultured cells derived from humans and mice but from rats. Previously, we reported that the discrepancies in heat shock-induced HO-1 expression in different animal species were caused by the access of heat shock factor 1 (HSF1) to heat shock element (HSE) in the different region of the HO-1 gene. Recently, we found that the human monocyte-derived cell line THP-1, which has been extensively used to study monocyte/macrophage functions, represents the heat shock induction of HO-1 after differentiation to macrophage-like cells, although not responsible before differentiation. In this study, we demonstrated that heat shock loading to macrophage-like cells derived from THP-1 specifically activated HSF1 to bind to HSE in the promotor region in the HO-1 gene, resulting in the induction of HO-1. Our finding is significant in understanding the regulation system by macrophages for inflammation caused by oxidative insults and associated with hyperthermia in vivo.