Leukotriene C_4 in Combination with Transforming Growth Factor-β Augments Extracellular Matrix Production from Human Lung Fibroblasts
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概要
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Airway remodeling has an important role in the pathogenesis of bronchial asthma and is associated with severe, intractable disease. A lot of mediators, especially cysteinyl leukotrienes (CysLTs) and transforming growth factor (TGF)-β that influence pathophysiology of bronchial asthma are involved in the formation of airway remodeling. We hypothesized that responsiveness of fibroblasts to CysLTs is not the same as that of activated myofibroblasts induced by TGF-β. We examined the effects of leukotriene C_4 (LTC_4) on collagen production from fibroblasts and myofibroblasts transformed by TGF-β. Furthermore, we investigated mRNA expression of CysLTl receptor and a-smooth muscle actin (α-SMA) as a marker of myofibroblast. TGF-β_1 stimulated collagen production from human fetal lung fibroblasts (HFL-1), but LTC_4 alone did not. Meanwhile, LTC_4 in combination with TGF-β_1 enhanced collagen production as compared with TGF-β alone. Real time PCR revealed that stimulation with TGF-β significantly upregulated CysLTIR and α-SMA mRNA expression in HFL-1. LTC_4 increased the collagen production through upregulation of CysLTIR induced by TGF-β. In the TGF-β-rich milieu such as asthma, activated myofibroblasts expressing CysLTIR can respond to CysLTs and produce abundant extracellular matrix thereby forming airway remodeling. These data suggest that leukotriene receptor antagonists may be an effective therapeutics for preventing airway remodeling in asthmatics.
- 獨協医科大学の論文
- 2004-03-25
著者
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Ishii Yoshiki
Department Of Pulmonary Medicine Jichi Medical School
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Asakura Takuma
Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine
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Chibana Kazuyuki
Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine
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Ishii Yoshiki
Department Of Biology Faculty Of Science Kobe University
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Asakura Takuma
Department Of Pulmonary Medicine And Clinical Immunology Dokkyo University School Of Medicine
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Chibana Kazuyuki
Department Of Pulmonary Medicine And Clinical Immunology Dokkyo University School Of Medicine
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