Effect of Montelukast, a Cysteinyl Receptor Antagonist, on Myofibroblasts in Interstitial Lung Disease

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Abstract

Montelukast, a potent cysteinyl receptor antagonist, may be an antifibrotic therapeutic agent for lung fibrosis. Seven sarcoidosis patients and 10 with unusual interstitial pneumonia underwent conventional bronchoalveolar lavage, from which myofibroblasts were recovered. Myofibroblast proliferation was assayed, alpha smooth muscle actin levels were measured, TGFβ mRNA RT-PCR transcripts were semiquantitated, and secretion was evaluated in myofibroblast supernatants. Montelukast at 10−8 M concentration had a suppressive effect on cell proliferation (31 ± 18%), which was significantly enhanced by LTD4 10−8 M. No differences were found between sarcoidosis (31.28 ± 15.9%) and unusual interstitial pneumonia (30.56 ± 24.3%) lines. Fetal calf serum (20%) produced an enhancing effect (29.8 ± 21.6%) in all lines. Myofibroblasts recovered from sarcoidosis patients showed lower α-smooth muscle actin contents than unusual interstitial pneumonia lines (0.09 ± 0.02 vs. 0.34 ± 0.16, p = 0.039, respectively). Montelukast suppressed α-actin in short-term cultures in sarcoidosis myofibroblasts and in long-term unusual interstitial pneumonia myofibroblasts. Montelukast at 10−6 M concentratin decreased the TGFβ-induced α-actin expression in all lines tested. Montelukast decreased mRNA expression of TGFβ. Montelukast may be a therapeutic agent in pathological conditions involving fibrotic and remodeling processes.

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