The role of interleukin-4 and interleukin-13 in the non-immunologic aspects of asthma pathogenesis.
Bronchial asthma is a complex disease characterized by airway inflammation involving a Th2-cytokine, interleukin (IL)-13. A substantial body of evidence has accumulated pointing to the pivotal role of IL-13 in the pathogenesis of bronchial asthma. The evidence is categorized as (i) analyses of mouse models, (ii) expression of these cytokines in the bronchial lesions, and (iii) genetic association of the signaling molecules of these cytokines. In addition, the molecular mechanism of the signal transduction of IL-13 has also been well characterized. We have applied microarray analyses to human bronchial epithelial cultures to search for genes regulated by IL-13 and have identified a subset of disease-relevant genes by comparison with cDNA libraries derived from normal and asthmatic bronchial biopsies. Expression of squamous cell carcinoma antigen-1 (SCCA1) and SCCA2, the cysteine and serine protease inhibitors, respectively, was the highest in the bronchial epithelial cells stimulated by IL-4 and IL-13 and was augmented in the asthmatic cDNA library. 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 bronchial asthma, and measuring its serum level may be relevant for diagnosing or monitoring the status of bronchial asthma.
Izuhara
Kenji
K
Division of Medical Biochemistry, Department of Biomolecular Sciences, Center for Comprehensive Community Medicine, Saga Medical School, Saga, Japan. kizuhara@post.saga-med.ac.jp
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000276:immunology*; D008954:Models, Biological; D018123:Receptors, Interleukin / Q000276:immunology; D053660:Receptors, Interleukin-13; D015398:Signal Transduction
C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D015847:Interleukin-4