IL-13 induces a bronchial epithelial phenotype that is profibrotic.
IL-13 induces a bronchial epithelial phenotype that is profibrotic.
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DOI：
10.1186/1465-9921-9-27
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发表时间：
2008-03-18
影响因子：
5.8
通讯作者：
George SC
中科院分区：
文献类型：
--
作者：
Malavia NK;Mih JD;Raub CB;Dinh BT;George SC
炎性细胞因子（如IL-13）和上皮的机械扰动（如刮伤）释放促纤维化因子，如TGF-β2，进而刺激哮喘中的上皮下纤维化。我们假设长时间的IL-13暴露会产生一种可塑性上皮表型，这种表型通过持续分泌刺激上皮下纤维化水平的可溶性介质而促纤维化。正常人支气管上皮细胞（NHBE）在分化期间在气-液界面处用IL-13（0、0.1、1或10 ng/ml）处理14天（接种后第7天至第21天），然后取出1天或7天。在第22-25天或第28-31天期间，将预处理和未处理的NHBE与包埋在大鼠尾胶原凝胶中的正常人肺成纤维细胞（NHLF）共培养3天。在NHBE中，IL-13在第22天和第28天诱导MUC 5AC蛋白和TGF-β2水平增加，而β-微管蛋白IV水平降低。在IL-13预处理的NHBE共培养物中，TGF-β2、培养基中的可溶性胶原、基质中的盐溶性胶原和来自基质中的纤维状胶原的二次谐波产生（SHG）信号在第25天升高，但在第31天没有升高。TGF-β2中和抗体逆转了胶原蛋白含量和SHG信号的增加。长时间的IL-13暴露，随后撤回产生上皮表型，其以增加胶原分泌的水平持续分泌TGF-β2，并改变底层成纤维细胞包埋的胶原基质的整体光学性质。IL-13从上皮中的延长的撤出，随后共培养不刺激纤维化，表明培养的气道上皮的可塑性和返回到基线的能力。因此，IL-13可能通过刺激气道上皮细胞分泌具有生物学意义的TGF-β2而促进哮喘中的上皮下纤维化。
Inflammatory cytokines (e.g. IL-13) and mechanical perturbations (e.g. scrape injury) to the epithelium release profibrotic factors such as TGF-β2, which may, in turn, stimulate subepithelial fibrosis in asthma. We hypothesized that prolonged IL-13 exposure creates a plastic epithelial phenotype that is profibrotic through continuous secretion of soluble mediators at levels that stimulate subepithelial fibrosis. Normal human bronchial epithelial cells (NHBE) were treated with IL-13 (0, 0.1, 1, or 10 ng/ml) for 14 days (day 7 to day 21 following seeding) at an air-liquid interface during differentiation, and then withdrawn for 1 or 7 days. Pre-treated and untreated NHBE were co-cultured for 3 days with normal human lung fibroblasts (NHLF) embedded in rat-tail collagen gels during days 22–25 or days 28–31. IL-13 induced increasing levels of MUC5AC protein, and TGF-β2, while decreasing β-Tubulin IV at day 22 and 28 in the NHBE. TGF-β2, soluble collagen in the media, salt soluble collagen in the matrix, and second harmonic generation (SHG) signal from fibrillar collagen in the matrix were elevated in the IL-13 pre-treated NHBE co-cultures at day 25, but not at day 31. A TGF-β2 neutralizing antibody reversed the increase in collagen content and SHG signal. Prolonged IL-13 exposure followed by withdrawal creates an epithelial phenotype, which continuously secretes TGF-β2 at levels that increase collagen secretion and alters the bulk optical properties of an underlying fibroblast-embedded collagen matrix. Extended withdrawal of IL-13 from the epithelium followed by co-culture does not stimulate fibrosis, indicating plasticity of the cultured airway epithelium and an ability to return to a baseline. Hence, IL-13 may contribute to subepithelial fibrosis in asthma by stimulating biologically significant TGF-β2 secretion from the airway epithelium.
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影响因子：
5.8
作者：
Keating, Dominic T.;Sadlier, Denise M.;Patricelli, Andrea;Smith, Sinead M.;Walls, Dermot;Egan, Jim J.;Doran, Peter P.
通讯作者：
Doran, Peter P.
影响因子：
6.1
作者：
Batra, V;Musani, AI;Peters, SP
通讯作者：
Peters, SP
影响因子：
6
作者：
Chu, HW;Balzar, S;Wenzel, SE
通讯作者：
Wenzel, SE
影响因子：
--
作者：
Agarwal, A;Coleno, ML;George, SC
通讯作者：
George, SC
DOI：
10.1513/pats.2306034
发表时间：
2004-01-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Holgate, Stephen T;Holloway, John;Davies, Donna E
通讯作者：
Davies, Donna E