A synthetic 10-kD heat shock protein (hsp10) from Mycobacterium tuberculosis modulates adjuvant arthritis.
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.
Ragno
S
S
The Inflammation Research Group, ARC Bone & Joint Research Unit, The London Hospital Medical College, London, UK.
Winrow
V R
VR
Mascagni
P
P
Lucietto
P
P
Di Pierro
F
F
Morris
C J
CJ
Blake
D R
DR
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology* / Q000494:pharmacology*; D018835:Chaperonin 10 / Q000276:immunology* / Q000494:pharmacology*; D005260:Female; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D012680:Sensitivity and Specificity
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D018835:Chaperonin 10; D010446:Peptide Fragments