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

Abstract

AbstractObjectives: 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.

Key Biomarkers