Hsp60 in inflammation and autoimmunity

Abstract

The canonical functions of the chaperone system (CS) are directed to maintaining protein homeostasis and preventing/counteracting the deleterious effects of stress. However, components of the CS if quali- or quantitatively abnormal, or in certain locations, can be etiopathogenic and cause diseases, the chaperonopathies. The molecular chaperone Hsp60 is one of the chief components of the CS known to be etiopathogenic in various disorders. In this chapter, the etiopathogenic role of Hsp60 in inflammatory and autoimmune conditions is discussed, as well as its participation in virus-induced diseases by helping the virus goes through its infectious cycle accompanied by inflammation and autoimmunity. The Hsp60 etiopathogenic mechanisms discussed include molecular mimicry; autoimmune and chronic inflammatory diseases as chaperonopathies by mistake or collaborationism; and facilitation of virus cycle and pathogenicity. Hsp60 is a potent antigen that can elicit autoantibodies. Hsp60 shares sequence and structural similarities with orthologs from different species and, thus, in extracellular locations, it cross-reacts with antibodies and immune cells activated by foreign immunogens. Hsp60 can also stimulate production of proinflammatory cytokines. Hsp60 can induce innate TLR4- and TLR2-mediated activation of T and B cells, acting as a link between innate and adaptive immunities. Together, the data show that Hsp60 plays a determinant etiopathogenic role in a variety of diseases and, therefore, should be targeted for therapy, specifically negative chaperonotherapy. This consists of strategies and means aiming at eliminating the chaperonin by silencing its gene or blocking/inhibiting the Hsp60 protein molecule.