Heat shock proteins and regulation of cytokine expression.

KEY WORDS heat shock proteins; cytokines; heat shock factor t has become clear in recent years that, heat shock proteins (hsps) play a major role in the acute in-flammatory response and inflammatory diseases. 1,z Heat shock proteins were originally characterized as a highly conserved group of proteins involved in the response of cellular organisms to stresses such as heat shock. 3,4 These proteins appear to have acquired more specialized roles within the immune response in higher eukaryotes. Heat shock proteins released into the circulation from infectious. organisms or host cells can induce cytokine release from monocytes and provoke an immune response. In addition, induction of the heat shock response and the intracellular accumulation of hsps appears to play an anti-inflammatory role in monocytes and macrophages, reducing the expression of cytokines and other pro-inflammatory molecules. 6-11 Tran-scriptional activation of the heat shock response involves the induction of heat shock factor (HSF), a sequence-specific transcription factor that binds to heat shock elements (HSE) in the promoters of heat shock genes, le,13 Mammalian cells contain a structurally-related family of HSF genes, each of which binds to HSE. 13 Heat shock factor-1 (HSF1), the best characterized family member, is a constitutive protein expressed as a monomer in the cytoplasm that migrates to the nucleus when stressed, forms a homotrimer, and binds to the promoters of heat shock genes. 14,1s In this manuscript, we aim to explore mechanisms involved in tran-scriptional repression of cytokine genes by molecular components of the mammalian heat shock response including hsps and HSF1.