Relationship between heat shock protein induction and the binding of antibodies to the extractable nuclear antigens on cultured human keratinocytes.
The importance of environmental factors such as ultraviolet light and temperature in the pathogenesis of cutaneous lupus erythematosus is well recognized. Recent evidence suggests the presence of autoantibodies to heat shock proteins (HSP) in the sera and enhanced expression of the HSP70 gene in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. We designed experiments to determine how HSP or stress protein inducers affect the cell surface binding of IgG antibodies from sera containing anti-SS-A/Ro and anti-ribonuclear protein (RNP) antibodies to keratinocytes because these antibodies are considered to be one of the immunologic triggers of cutaneous lupus erythematosus. Immunofluorescence and immunoblot analysis using a monoclonal antibody to the 72 kDa of HSP revealed that an 18-h incubation with 10 micrograms/ml of delta 12-PGJ2, one of cytotoxic prostaglandins, induced HSP72 formation in cultured human keratinocytes. delta 12-PGJ2 augmented the binding of IgG antibodies from sera containing anti-U1RNP and anti-SS-A/Ro antibodies to cultured keratinocytes, but produced no enhancement of the binding of IgG antibodies from sera containing anti-Sm or anti-DNA antibodies. Similar results were also obtained by using flow cytometry analysis. HSP was also induced by ultraviolet B irradiation. These results suggest that exposure of keratinocytes to stressors such as delta 12-PGJ2 and ultraviolet light increases the binding sites for U1RNP,SS-A/Ro, and SS-B/La antibodies. The association between HSP induction and the appearance of extractable nuclear antigens may provide a better understanding of why environmental stimuli can promote the development of erythematous lesions in the skin.
Furukawa
F
F
Department of Dermatology, Faculty of Medicine, Kyoto University, Japan.
Ikai
K
K
Matsuyoshi
N
N
Shimizu
K
K
Imamura
S
S
D034961:Antigens, Nuclear; D001323:Autoantibodies / Q000378:metabolism; D001666:Binding Sites, Antibody; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007231:Infant, Newborn; D015603:Keratinocytes / Q000276:immunology*; D008297:Male; D009687:Nuclear Proteins / Q000097:blood / Q000276:immunology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology
D034961:Antigens, Nuclear; D001323:Autoantibodies; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D009687:Nuclear Proteins; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2