Chaperokine-induced signal transduction pathways.
A turning point in understanding the function of heat shock proteins (HSP) on components of the immune system has now begun. From their original description as intracellular molecular chaperones of naïve, aberrantly folded or mutated proteins and primarily involved in cytoprotection in response to stressful stimuli, in recent years, new functions of HSP have been revealed. Strong evidence now exists demonstrating that the seventy-kDa heat shock protein (HSP70) exits mammalian cells not only following necrotic cell death but also by a process involving its active release in response to stresses including cytokines, acute psychological stress and exercise. The released extracellular HSP70 interacts with cells of the immune system and exerts immunoregulatory effects--known as the chaperokine activity of HSP70. The chaperokine activity of HSP70 is mediated in part by utilizing surface receptors for both Toll-like receptor-2 (TLR2; receptor for Gram-positive bacteria) and TLR4 (receptor for Gram-negative bacteria) in a CD14-dependent fashion. These findings suggest an important role for heat shock proteins in host protection against pathogenic infection. This review will briefly discuss chaperokine-induced signaling and its relevance to infection and exercise.
Asea
Alexzander
A
Center for Molecular Stress Response, Boston University Medical Center, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA. aasea@medicine.bu.edu
D000818:Animals; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D018840:HSP70 Heat-Shock Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors