Original Articles: Mechanisms Of AllergyIL-4 and IL-13 induce myofibroblastic phenotype of human lung fibroblasts through c-Jun NH2-terminal kinase–dependent pathway☆,☆☆
Section snippets
Reagents
SB 203580 and PD 98059 were obtained from Carbiochem-Novabiochem Corporation (La Jolla, Calif) and New England Biolabs, Inc (Beverly, Mass). Anti–TGF-β1 antibody, anti–IL-4 antibody, and anti–IL-13 antibody were obtained from Genzyme TECHNE (Minneapolis, Minn). CEP-1347 was kindly provided by Cephalon Incorporated (West Chester, Pa). SB 203580, PD 98059, and CEP-1347 were dissolved in dimethylsulfoxide (DMSO).
Cell cultures
HLFs were obtained from Clonetics (San Diego, Calif). In the preliminary experiments
IL-4 and IL-13 induce increases in α-smooth muscle actin expression
The expression of α-smooth muscle actin in IL-4– and IL-13–stimulated HLFs increased in a dose-dependent manner (Fig 1, A-C ) and in a time-dependent manner (Fig 1, D-F ).
Discussion
In the present study we examined the role of IL-4 and IL-13 in inducing the phenotypic modulation of HLFs to myofibroblasts and analyzed the intracellular signal–inducing myofibroblastic phenotype of HLF characterized by the expression of α-smooth muscle actin. The results showed the following: (1) IL-4 and IL-13 induced the phenotypic modulation of HLFs to myofibroblasts in a dose- and time-dependent manner; (2) anti–TGF-β1 antibody did not affect IL-4– and IL-13–induced phenotypic modulation
Acknowledgements
We thank Dr Yuzuru Matsuda (Kyowa-Hakko Kogyo Company, Limited) and Dr Jeffery Vaught and Dr Matthew Miller (Cephalon Incorporated) for the generous gift of CEP-1347.
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Supported in part by a Grant-in-Aid for High-Tech Research Center from the Japanese Ministry of Education, Science, Sports, and Culture to Nihon University.
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Reprint requests: Shu Hashimoto, MD, First Department of Internal Medicine Nihon University School of Medicine, 30-1 Oyaguchikamimachi, Itabashi-ku, Tokyo 173-8610, Japan.