Clarification of the mechanism of allergic diseases based on the analyses of the mechanism of signal transduction of interleukin-4 and-13

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Although it is well known that interleukin(IL)-4 and IL- 13 are involved in the pathogenesis of allergic diseases, the precise mechanism of these diseases is still obscure. To clarify this point, we previously identified IL-4- or IL-13-inducible genes in bronchial epithelial cells by the microarray approach. We demonstrated that expression of the squamous cell carcinoma antigen(SCCA) 1 and SCCA2 included in the identified genes was augmented in the bronchial tissues and the serum derived from asthma patients. In this study, we analyzed the functional roles of SCCA1 and SCCA2.Although SCCA1 and SCCA2 belong to the serpin family, we found that these molecules inhibited cysteine proteases, in contrast to other serpins. Particularly, it is of note that we showed that SCCA2 inhibited the cysteine proteinase activity of Der p 1,a major mite allergen. These results indicated that IL-4 and IL-13 play a role in the defense mechanism against external cysteine proteinases by inducing cysteine proteinase inhibitors. Furthermore, we succeeded in generating a SCCA2 mutant whose inhibitory activity against Der p 1 was stronger than the wild SCCA2. These results indicated the possibility that we may apply SCCA2 itself or its analogue to development of a reagent against allergic diseases induced by mites.