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Dual Action of TGF-β1 on Nasal-Polyp Derived Fibroblasts

Authors

  • Stewart C. Little MD,

    Corresponding author
    1. Department of Otolaryngology–HNS, University of Virginia Health System, Charlottesville, VA, U.S.A.
    • Stewart C. Little, MD, Department of Otolaryngology-HNS, Box 800713, University of Virginia Health System, Charlottesville, VA 22908, U.S.A.
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  • S Brandon Early,

    1. Asthma and Allergic Disease Center, Beirne Carter Center for Immunology, Department of Medicine, University of Virginia Health System, Charlottesville, VA, U.S.A.
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  • Charles R. Woodard MD,

    1. Department of Otolaryngology–HNS, University of Virginia Health System, Charlottesville, VA, U.S.A.
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  • David C. Shonka Jr MD,

    1. Department of Otolaryngology–HNS, University of Virginia Health System, Charlottesville, VA, U.S.A.
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  • Joseph K. Han MD,

    1. Division of Rhinology, Endoscopic Sinus and Skull Base Surgery, Department of Otolaryngology and Head & Neck Surgery, Eastern Virginia Medical School, Norfolk, Virginia, U.S.A.
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  • Larry Borish MD, PhD,

    1. Asthma and Allergic Disease Center, Beirne Carter Center for Immunology, Department of Medicine, University of Virginia Health System, Charlottesville, VA, U.S.A.
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  • John W. Steinke PhD

    1. Asthma and Allergic Disease Center, Beirne Carter Center for Immunology, Department of Medicine, University of Virginia Health System, Charlottesville, VA, U.S.A.
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  • Stewart C. Little, MD, and S. Brandon Early contributed equally to this work.

  • This research was supported by NIH AI01793 and AI/HL47737.

Abstract

Objectives: Transforming growth factor β-1 (TGF-β1) is a known fibrogenic factor with immunosuppressive properties. We wanted to determine the effect of stimulation with TGF-β1 on nasal polyp-derived fibroblasts and assess the role this molecule would have in polyp formation and growth.

Study Design: Nasal-polyp derived fibroblasts were cultured with or without TGF-β1, and proliferation and cytokine secretion were measured.

Methods: Fibroblasts were isolated from nasal polyps following endoscopic surgery. Cells were plated and grown until confluent, after which they were split and used in assays. Cells were stimulated with TGF- β1 and mRNA collected after 16 hours, supernatants after 72 hours, and proliferation measured after 96 hours of culture.

Results: TGF-β1 significantly (P < .02) increased proliferation of nasal-polyp derived fibroblasts. We examined the expression of inflammatory cytokines and found that TGF-β1 decreased expression of CCL2 (MCP-1), CCL5 (RANTES), CCL11 (eotaxin), granulocyte-colony stimulating factor (G-CSF), and GM-CSF (P < .05). In contrast, incubation with TGF-β1 increased fibronectin, procollagen, vascular endothelial growth factor (VEGF), and TGF-β2 protein production (P < .05). For select samples, we confirmed that the increased protein production was due to increased mRNA expression.

Conclusion: These studies suggest that TGF-β1 expression in polyp tissue can have dual effects. One role is to act as an anti-inflammatory agent shown by the ability to inhibit pro-inflammatory mRNA and protein production. At the same time, TGF-β1 expression leads to increases in factors involved in fibrosis and angiogenesis, promoting remodeling and cell growth.

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