Hormone 1 alpha,25-dihydroxyvitamin D3 modulates heat shock response in monocytes

Abstract

Monocytes, which play a central role in inflammatory reactions, are exposed to elevated temperatures in febrile states or to potential cellular toxins (e.g., reactive oxygen species, immune mediators). We analyzed the heat shock (HS) response in human peripheral blood monocytes and the monocytic line U937 compared with that in dermal fibroblasts. After HS, U937 cells and fibroblasts synthesized mainly the 70- and 83-kDa HS proteins (HSPs), whereas the spectrum of HSPs synthesized by monocytes varied over the range 41-45 degrees C. Incubation with hydrogen peroxide induced synthesis of the 70-kDa HSP in monocytes only. The hormone 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] that protects monocytes from thermal injury had similar effects on the HS response in U937 cells, increasing synthesis of HSPs and levels of HSP 70 mRNA and partially preventing the decrease in normal protein synthesis, whereas interferon-gamma had no effect. 1,25-(OH)2D3 did not modify the HS response in fibroblasts, although these cells contained cellular receptors for 1,25-(OH)2D3. 1,25-(OH)2D3 could play a specific role in modulating the HS response in monocytes and related cells.