Herrera-Esparza Rafael, Villalobos Ricardo, Bollain-Y-Goytia Juan-Jose, Ramírez-Sandoval Roxana, Sánchez-Rodriguez Sergio H, Pacheco-Tovar Guadalupe, Avalos-Diaz Esperanza
Department of Immunology, Centro de Biología Experimental, Universidad Autónoma de Zacatecas, Zacatecas, Mexico.
Clin Dev Immunol. 2006 Jun-Dec;13(2-4):163-6. doi: 10.1080/17402520600876796.
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/cm(2)) 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.
在亚急性皮肤型红斑狼疮(SCLE)中,皮肤抗原是Ro和La自身抗原的主要来源。本研究的目的是证明紫外线是否会增加皮肤中Ro自身抗原的可及性,同时评估半胱天冬酶抑制剂Ac-DEVD-CMK的阻断作用。为此,对新生Balb/c小鼠进行紫外线B(UVB)照射(5 - 30 mJ/cm²),相当于中度至重度晒伤。给动物注射来自SCLE患者的单克隆抗Ro抗体。通过注射抗Fas抗体也可诱导细胞凋亡。通过直接免疫荧光、TUNEL法以及逆转录聚合酶链反应(RT-PCR)检测半胱天冬酶3的表达来检查皮肤样本。本研究的主要发现如下:1. UVB照射和抗Fas可诱导角质形成细胞凋亡。2. 细胞凋亡使Ro抗原重新分布于细胞表面,且Ro抗体能更好地触发细胞凋亡。3. 半胱天冬酶3抑制剂Ac-DEVD-CMK可降低表皮中Ro自身抗原的可及性,并阻止抗Ro的沉积。总之,阻断半胱天冬酶途径可避免抗Ro在皮肤中的沉积;这一发现为SCLE患者的治疗提供了一个前景。