No abstract

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.

No abstract

Fas ligand (L) is a membrane protein from the tumor necrosis factor (TNF) family. It induces apoptosis upon contact with its Fas/CD95/APO1 receptor. Trimerization of FasL on the surface of effector cells is essential in the binding of the Fas trimer of the target cells. The receptor then recruits an adaptor and caspase-like proteins which lead apoptosis. This paper reports on the fate of FasL in HEp-2 cells committed to apoptosis by induction with campthotecin. Our main results demonstrated that in non-apoptotic cells, FasL aggregates in the cytoplasm forming trimers of 120 kDa. Apoptosis increases the trimeric FasL species, but also induces its dissociation into monomers of 35 kDa. In conclusion, camptothecin appears to perturb the Fas and FasL segregation in the cytoplasm by promoting the transit of FasL to the cell surface, thus fostering a process of autocrine or paracrine apoptosis. FasL is trimerized prior to Fas/FasL complex formation, and after apoptosis, FasL undergoes an intense turnover.

En los pacientes que desarrollan lupus, su sistema inmune se activa y se vuelve contra el mismo huésped, por lo que es considerada una enfermedad autoinmune. En los Estados Unidos, existe más de un millón de personas que presenta Lupus. Sus síntomas aparecen en una gran variedad de formas, en los cuales la mitad de los casos es letal. El daño aparece en cualquier órgano del cuerpo y puede causar artritis con inflamación, fatiga, eritema en alas de mariposa en región malar, úlceras orales, fotosensibilidad, serositis (inflamación del tejido alrededor del corazón y pulmón), osteoporosis, desórdenes renales (proteinuria y destrucción celular), desórdenes sanguíneos (leucopenia, linfopenia, trombocitopenia, anemia hemolítica), desórdenes inmunológicos (anticuerpos anti-DNA y anti-Sm) y títulos de anticuerpos antinucleares anormales. Utilizando técnicas de biología molecular, se han descubierto algunos factores que regulan el sistema inmune, así como mecanismos bioquímicos por los cuales en el lupus se presenta daño al tejido. También se han identificado algunos genes candidato que parecen estar involucrados en el lupus.