Anti-HSP auto-antibodies enhance HSP-induced pro-inflammatory cytokine production in human monocytic cells via Toll-like receptors.
Auto-antibodies against heat shock proteins (HSPs) are frequently found in the sera of patients with rheumatic and other autoimmune diseases. However, it is unclear whether these auto-antibodies play a role in the pathophysiology and etiology of these diseases. We found that a murine anti-HSP60 mAb enhanced the production of IL-8 and tumor necrosis factor-alpha induced by human HSP60 in the human monocytic cell lines THP-1 and U937, and human peripheral blood monocytes. Similar enhancement was observed with the combination of human HSP70 protein and a murine anti-HSP70 mAb. The enhancing effects were also observed for F(ab')2 fragment, but not for monovalent Fab fragment. This suggests that the enhancement is due to cross-linking of HSP by the anti-HSP antibodies. The induction of IL-8 was dramatically suppressed by the transfection of a dominant-negative mutant of Toll-like receptor 4. We also found that sera from patients with rheumatic autoimmune diseases, which contained higher anti-HSP60 auto-antibody titers than sera from healthy donors, significantly enhanced the IL-8 production induced by human HSP60 in THP-1 cells. We propose that auto-antibodies against HSPs have the potential to play a pathogenic role in rheumatic autoimmune diseases by enhancing inflammatory reactions.
Department of Microbiology, Sapporo Medical University School of Medicine, South-1, West-17, Sapporo 060-8556, Japan.
Shin-ichi
S
Yokota
Seiji
S
Minota
Nobuhiro
N
Fujii
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001323:Autoantibodies; D016207:Cytokines; D006360:Heat-Shock Proteins; D016209:Interleukin-8; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha