Elucidation of molecular mechanism for allergic disease, focusing on p38 MAP Kinase.

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We conducted the following two research projects.I)To elucidate the new molecular mechanism of allergic skin disease, a direct interaction between p38 MAPK and FK506-binding protein (FKBP) was investigated. However, the regulation of p38 MAPK by the direct interaction with FKBP was not confirmed. In the process of this project, we successfully identified three new spliced transcripts of FKBP-12 and investigated their tissue-specific expression (submitted to Gene).II)To elucidate the molecular mechanism for allergic lung disease, p38α-KO mice and transgenic mice in which p38 dominant-negative form is expressed in a lung-specific manner (p38d.n.-TG) were subjected to bleomycin administration. Bleomycin, anti-cancer drug is known to induce interstitial lung disease as a side effect. We investigated a static compliance of the lung from wild, p38α-KO and p38d.n.-TG mice two weeks after l, t, bleomycin administration. The static compliance of the lung from bleomycin-administered wild mice was significantly decreased compared that from saline-administered wild mice. In contrast, the bleomycin-induced decrease in static lung compliance was not observed in case of p38α-KO and p38d.n-TG, suggesting that p38α is involved in bleomycin-induced interstitial lung disease. We are further investigating this point.