A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice.
Previous studies have established that Mycobacterium tuberculosis heat shock protein 65 (mHSP65) plays an important role in immune-associated diseases as an autoimmune factor. Some overlapping epitopes of mHSP65 may serve as initiators of both atherosclerosis and other autoimmune-associated diseases. In the present study, atherosclerosis was significantly enhanced in high-cholesterol diet (HCD)-fed New Zealand white rabbits immunized with mHSP65(91-105) compared with PBS-immunized or BSA-immunized rabbits. Immunizing wild-type C57BL/6J mice with mHSP65(91-105) induced the aortic endothelial injury. Although western blot demonstrated that specific antibodies against mHSP65(91-105) can cross-react with recombinant human heat shock protein 60, specific antibodies against mHSP65(91-105) had no direct effects on HUVECs in vitro. Laser scanning confocal microscopy showed that mHSP65(91-105) localized in the cytoplasm of HUVECs, even when HUVECs were heat shocked at 42°C. mHSP65(91-105)-specific splenic cells secreted more IFN-γ than controls. Also, adoptive transfer of mHSP65(91-105)-specific splenic cells can accelerate atherosclerosis in ldlr( -/- ) mice. We can conclude that the (auto)immune response to mHSP65(91-105) accelerates atherosclerosis in animal models, and that the response of Th1 plays an important role in this progress.
Department of Pharmacology, School of Pharmacy, Nanjing Medical University, 210029 Nanjing, China.
Yu
Y
Zhang
Qiyan
Q
Xiong
Xiangbing
X
Hu
Yunxiao
Y
Sun
Xiying
X
Tan
Huiyong
H
Zhang
Yong
Y
Lu
Jingjing
J
Liu
D019264:Adoptive Transfer; D000818:Animals; D001018:Aortic Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001426:Bacterial Proteins / Q000276:immunology*; D015153:Blotting, Western; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000276:immunology*; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D000939:Epitopes; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011817:Rabbits; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D013997:Time Factors
D001426:Bacterial Proteins; D018834:Chaperonin 60; D002791:Cholesterol, Dietary; D000939:Epitopes; D010446:Peptide Fragments; D011973:Receptors, LDL; C074119:heat-shock protein 65, Mycobacterium