A synthetic 10-kD heat shock protein (hsp10) fromMycobacterium tuberculosismodulates adjuvant arthritis

Abstract

The heat shock protein, hsp10, is an abundant protein in Mycobacterium tuberculosis (Mtb), its nucleotide sequence encoding a protein of 99 amino acids with a molecular mass of 10.7 kD. This sequence is phylogenetically conserved, being represented by the GroES homologue of Escherichia coli. Hsp10 and GroES are members of the chaperonin 10 family of molecular chaperones, and GroEs is necessary for the optimal activity of GroEL, a member of the chaperonin 60 family and the E. coli homologue of mycobacterial hsp65. Since hsp65 has been implicated in both experimental and human rheumatoid arthritis, we aimed to assess the immunomodulatory effects of its co-chaperonin, hsp10, in experimental arthritis. Our results show that an aqueous solution of a mycobacterial hsp10 delayed the onset and severity of adjuvant-induced arthritis in rodents when administered after disease induction but before joint involvement occurred. This biological activity was specific for the hsp10 of Mtb, since neither GroES not the rat homologue was effective. Using synthetic hsp10 fragments, the activity was localized to the N-terminal region of the molecule. Assessment of circulating antibody levels to mycobacterial hsp10 and hsp65 indicated that all arthritic rats had increased titres to both hsp10 and hsp65: hsp10-treated rats showed further elevation of this humoral response not only to hsp10 but also to hsp65 when compared with the untreated arthritic control. This is the first report of the immunomodulatory activity of mycobacterial hsp10 in experimental arthritis, and exhibits a potential role for this co-chaperonin in pathophysiological situations.

Heat-shock proteins: Inflammatory versus regulatory attributes

“…Also, the Hsp10 treatment might show a beneficial effect in patients, but not necessarily in mouse models, and a reverse outcome might be observed for some other proteins. Hsp10 has been shown to induce suppression of AA (Ragno et al 1996;Agnello et al 2002), which further supports the rationale for testing of Hsp10 in RA patients. Similarly, Hsp10 has been shown to reduce clinical signs of experimental autoimmune encephalomyelitis (Johnson et al 2005), and therefore, it might also be of utility in the treatment of multiple sclerosis.…”

Heat shock protein 10 of Chlamydophila pneumoniae induces proinflammatory cytokines through Toll-like receptor (TLR) 2 and TLR4 in human monocytes THP-1

“…Reports on the other organisms also proved HSP10 may play a role in the inflammation-related immunopathogenic process (Ragno et al 1996;Henderson and Pockley 2010).…”

In-vitro effects of Mycobacterium bovis BCG-lysate and its derived heat shock proteins on cytokines secretion by blood mononuclear cells of rheumatoid arthritis patients in comparison with healthy controls

“…HSP60 and HSP70 have been studied and identified as immune targets in RA and some other inflammatory diseases. Although data on human diseases are still scattered and incomplete, a picture is emerging in which expression of HSPs or immune reactivity to HSPs seems to be associated with downregulation of inflammation, rather than with induction or propagation of inflammation [31][32][33].…”