Administration of M. leprae Hsp65 interferes with the murine lupus progression.
The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K(409)A recombinant Hsp65 of M. leprae in an animal model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F(1) mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The treatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F(1) serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K(409)A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule intervening in the progression of the SLE, and that the point mutated K(409)A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process.
Marengo
Eliana B
EB
Immunochemistry Laboratory, Instituto Butantan, São Paulo, Brazil.
de Moraes
Luciana V
LV
Faria
Marcella
M
Fernandes
Beatriz L
BL
Carvalho
Luciana V
LV
Tambourgi
Denise V
DV
Rizzo
Luiz V
LV
Portaro
Fernanda C V
FC
Camargo
Antônio Carlos M
AC
Sant'anna
Osvaldo A
OA
D000818:Animals; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000627:therapeutic use*; D018834:Chaperonin 60; D018833:Chaperonins / Q000627:therapeutic use*; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005921:Glomerulonephritis / Q000209:etiology / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000145:classification / Q000503:physiopathology* / Q000517:prevention & control*; D051379:Mice; D009166:Mycobacterium leprae
D001426:Bacterial Proteins; D018834:Chaperonin 60; C074119:heat-shock protein 65, Mycobacterium; D004247:DNA; D018833:Chaperonins