In subacute cutaneous lupus eryhematosus (SCLE) the cutaneous antigens constitute the main source of Ro and La autoantigens. The aim of this investigation was to demonstrate if UV light increases the availability of Ro autoantigen in the skin, also the blocking effect of Ac-DEVD-CMK a caspase inhibitor was assessed. For this purpose newborn Balb/c mice were UVB irradiated (5–30 mJ/cm2) equivalent to a moderate to severe sunburn. Animals were injected with monoclonal anti-Ro antibodies from SCLE patients. Apoptosis was also induced by anti-Fas antibody injection. Skin samples were examined by direct immunofluoresence, by TUNEL, and the expression of caspase 3 by RT-PCR. Major findings of present studies were: 1. UVB irradiation and anti-Fas induced apoptosis of keratinocytes. 2. Apoptosis redistribute the Ro antigen on cell surface and is better triggered by Ro antibody. 3. The caspase 3 inhibitor Ac-DEVD-CMK decreases the availability of Ro autoantigen in epidermis and prevents deposition of anti-Ro. In conclusion, the caspase pathway would be blocked to avoid anti-Ro deposition along skin; this finding would be a prospect in the treatment of SCLE patients.
The data indicate that functional iNOS activity is present in glomeruli as part of the inflammatory process in the kidney; therefore the products of iNOS could play a role in the pathogenesis of lupus nephritis.
Obiettivo. Lo scopo di questo studio è quello di indagare se l’apoptosis e la necrosi aumentano l’antigenicità delle proteine riconosciute da anticorpi antinucleo. Materiale e metodi. Cellule HEp-2 sono state coltivate in condizioni standard; l’apoptosis è stata indotta con camptecina e la necrosi con cloruro di mercurio. L’antigenicità delle proteine estratte dalle cellule è stato testata su membrane di nitrocellulosa e sondata con sieri positivi o negativi per anticorpi antinucleo utilizzando un sistema ELISA a luminescenza (luminescent). Risultati. Le alterazioni apoptotiche nelle cellule HEp-2 sono apparse entro 24 ore dall’esposizione alla camptoicina, mentre i segni di necrosi si sono evidenziati più precocemente. La luminescenza si è dimostrata significativamente superiore nei sieri ANA positivi che nei controlli ANA negativi. Gli antcorpi antinucleari sieirici riconoscono meglio gli antigeni da cellule apoptotiche e necrotiche rispetto ai controlli che non hanno subito trattamenti chimici. Conclusioni. L’apoptosi e la necrosi incrementano la capacità legante degli ANA attraverso una migliore disponibilità di antigeni intracellulari o svelando epitopi criptici
Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.
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