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IL-7 inhibits fibroblast TGF-β production and signaling in pulmonary fibrosis
Min Huang, … , Robert M. Strieter, Steven M. Dubinett
Min Huang, … , Robert M. Strieter, Steven M. Dubinett
Published April 1, 2002
Citation Information: J Clin Invest. 2002;109(7):931-937. https://doi.org/10.1172/JCI14685.
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Article Genetics

IL-7 inhibits fibroblast TGF-β production and signaling in pulmonary fibrosis

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Abstract

Based on studies by our group and others, we hypothesized that IL-7 may possess antifibrotic activities in an IFN-γ–dependent and independent manner. Here, we have evaluated the antifibrotic therapeutic potential of IL-7 in both in vitro and in vivo pulmonary fibrosis models. IL-7 inhibited both TGF-β production and signaling in fibroblasts and required an intact JAK1/STAT1 signal transduction pathway. IL-7–mediated inhibition of TGF-β signaling was found to be associated with an increase in Smad7, a major inhibitory regulator in the SMAD family. In the presence of IL-7, Smad7 dominant negative fibroblasts restored TGF-β–induced collagen synthesis, indicating that an IL-7–mediated increase in Smad7 suppressed TGF-β signaling. Consistent with these in vitro findings, recombinant IL-7 decreased bleomycin-induced pulmonary fibrosis in vivo, independent of IFN-γ. The antifibrotic activities of IL-7 merit further basic and clinical investigation for the treatment of pulmonary fibrosis.

Authors

Min Huang, Sherven Sharma, Li X. Zhu, Michael P. Keane, Jie Luo, Ling Zhang, Marie D. Burdick, Ying Q. Lin, Mariam Dohadwala, Brian Gardner, Raj K. Batra, Robert M. Strieter, Steven M. Dubinett

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Figure 1

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IL-7 decreases TGF-β production by PFF in an IFN-γ–independent manner. (...
IL-7 decreases TGF-β production by PFF in an IFN-γ–independent manner. (a andb) Primary fibroblasts from IPF patients (PFF, n = 5) or non-IPF subjects (NF, n = 5) were cultured in medium with or without IL-7 for 24 hours, and the culture supernatants were assayed for TGF-β by ELISA. IL-7 decreases TGF-β production in PFF, but not in NF. (c and d) While IFN-γ decreased TGF-β production in both NF and PFF, IL-7 decreased TGF-β production only in PFF. The addition of anti–IFN-γ antibody did not alter the capacity of IL-7 to decrease TGF-β, suggesting that IL-7 acts in an IFN-γ–independent manner. *P < 0.01.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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