Heat shock proteins and toll-like receptors.
Researchers have only just begun to elucidate the relationship between heat shock proteins (HSP) and Toll-like receptors (TLR). HSP were originally described as an intracellular molecular chaperone of naïve, aberrantly folded, or mutated proteins and primarily implicated as a cytoprotective protein when cells are exposed to stressful stimuli. However, recent studies have ascribed novel functions to the Hsp70 protein depending on its localization: Surface-bound Hsp70 specifically activate natural killer (NK) cells, while Hsp70 released into the extracellular milieu specifically bind to Toll-like receptors (TLR) 2 and 4 on antigen-presenting cells (APC) and exerts immunoregulatory effects, including upregulation of adhesion molecules, co-stimulatory molecule expression, and cytokine and chemokine release-a process known as the chaperokine activity of Hsp70. This chapter discusses the most recent advances in the understanding of heat shock protein (HSP) and TLR interactions in general and highlights recent findings that demonstrate Hsp70 is a ligand for TLR and its biological significance.
Asea
Alexzander
A
Division of Investigative Pathology,Texas A&M University System Health Science Center College of Medicine, 1901 South 1st Street, Temple, TX 76504, USA. aasea@swmail.sw.org
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018832:Molecular Chaperones / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism / Q000502:physiology*
D004731:Endotoxins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D051193:Toll-Like Receptors