Research on the mechanism of bullous diseases-Immunological and biological studies-

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We have been studied the function and structure of cutaneous basement membrane zone (BMZ), and the pathogenesis of autoimmune bullous diseases. We have been contributed to the solution of the pathogenesis of the disease on BMZ of the other organs (ex.mucous membrane etc.). We get the fruits as follows. (1) The study of signal transduction. It was reported the possibility of transmembrane signalling exerted by pemphigus IgG binding keratinocytes. We reported a transient increase of intracellular Ca^<2+> concentration ( [Ca^<2+>]i) induced by IgG from the patients with bullous pemphigoid (BP), and the inhibition of this increase by the addition of phospholipase C inhibitor (Autoimmunity, 1996). These results suggested the possibility of transmembrane signaling exerted by BP IgG binding keratinocyte. (2) The study of the role of IgG subclass in the pathogenesis of BP : We reported that BP IgG_1 mainly in duce a transient in crease of [Ca^<2+>]i, and BP IgG_2 and IgG_4 inhibit an increase … More of [Ca^<2+>]i induced by BP IgG_1 (Autoimmunity, 1996 and submitted). In pemphigus, it was reported that a switching of IgG subclass was observed, and the possibility that IgG_4 serves as blocking antibody. On the other hand, we reported that there was a low possibility of IgG subclass switching in BP (submitted). In BP,the main IgG subclass were IgG_1 and IgG_4. The anti-BMZ autibody IgG titer was correlated with anti-BMZ IgG_1 and IgG_4. (3) The study of structure of BMZ.We examined the origins of BMZ chondroitin sulfate proteoglycan of BMZ of dermal-epidermal junction and hair follicle epithelium are of epidermal origin (J.J.D., 1996). Then we contributed to the solution of the pathogenesis of epidermolysis bullous simplex associated with late-onset muscular dystrophy (Human Molecular Genetics, 1996). (4) The study of cell adhesion molecule in oral mucous membrane. We examined the expression and localization of adhesion molecules in human normal oral mucous, tongue and gingiva, immunohistochemically. Integrin alpha5 was detected only in mucous membrane but not in tongues and gingiva (Oral oncology, 1995). The distribution of integrin alpha2, alpha3, alpha6, beta1, beta3 and beta4, and E-cadherin, P-cadherin, desmoglain and ICAM-1 was no significant change among mucous membrane, tongue and gingiva. Less