Dual action of TGF-beta1 on nasal-polyp derived fibroblasts.
OBJECTIVES: Transforming growth factor beta-1 (TGF-beta1) is a known fibrogenic factor with immunosuppressive properties. We wanted to determine the effect of stimulation with TGF-beta1 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-beta1, 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- beta1 and mRNA collected after 16 hours, supernatants after 72 hours, and proliferation measured after 96 hours of culture. RESULTS: TGF-beta1 significantly (P < .02) increased proliferation of nasal-polyp derived fibroblasts. We examined the expression of inflammatory cytokines and found that TGF-beta1 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-beta1 increased fibronectin, procollagen, vascular endothelial growth factor (VEGF), and TGF-beta2 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-beta1 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-beta1 expression leads to increases in factors involved in fibrosis and angiogenesis, promoting remodeling and cell growth.
Little, SC; Early, SB; Woodard, CR; Shonka, DC; Han, JK; Borish, L; Steinke, JW
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