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Analysis of novel disease-related genes in bronchial asthma
Authors:Yuyama Noriko  Davies Donna E  Akaiwa Mina  Matsui Keiko  Hamasaki Yuhei  Suminami Yoshinori  Yoshida Ning Lu  Maeda Miyako  Pandit Anita  Lordan James L  Kamogawa Yumiko  Arima Kazuhiko  Nagumo Fumio  Sugimachi Mitsuhiko  Berger Ann  Richards Ivan  Roberds Steven L  Yamashita Tetsuji  Kishi Fumio  Kato Hiroshi  Arai Ken-ichi  Ohshima Koichi  Tadano Jutaro  Hamasaki Naotaka  Miyatake Shoichiro  Sugita Yuji  Holgate Stephen T  Izuhara Kenji
Institution:Genox Research, Inc. Kawasaki, Japan.
Abstract:Bronchial asthma is a complex disease characterized by airway inflammation involving interleukin (IL)-4 and IL-13. We have applied microarray analyses to human bronchial epithelial cultures to probe for genes regulated by these cytokines and have identified a subset of disease-relevant genes by comparison with cDNA libraries derived from normal and asthmatic bronchial biopsies. Squamous cell carcinoma antigen-1 (SCCA1) and SCCA2, the cysteine and serine protease inhibitors, respectively, showed the highest expression by IL-4 and IL-13, and particularly, SCCA1 was significantly increased in the asthmatic cDNA library. STAT6 was shown to be involved in expression of SCCA1 and SCCA2 in vitro. Furthermore, serum levels of SCCA were also elevated in asthmatic patients. Taken together, it was supposed that SCCA may play some role in the pathogenesis of bronchia asthma, and measuring its serum level may be relevant for diagnosing or monitoring the status of bronchial asthma. In a complex disorder such as asthma, this combination of in vitro and in vivo genomic approaches is a powerful discriminatory method enabling identification of novel disease-related genes and their mechanisms of regulation.
Keywords:bronchial epithelial cell/interleukin-4/interleukin-13/microarray/squamous cell carcinoma antigen
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