Induction of eotaxin production by interleukin-4, interleukin-13 and lipopolysaccharide by nasal fibroblasts
Induction of eotaxin production by interleukin-4, interleukin-13 and lipopolysaccharide by nasal fibroblasts
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DOI：
10.1111/j.1365-2222.2004.1954.x
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发表时间：
2004-05-01
影响因子：
6.1
通讯作者：
Yagi, T
中科院分区：
文献类型：
--
作者：
Nonaka, M;Pawankar, R;Yagi, T
背景 越来越多的证据表明嗜酸性粒细胞趋化因子是组织嗜酸性粒细胞增多的关键介质。成纤维细胞是嗜酸细胞趋化因子的主要来源。鼻息肉病、特应性皮炎和哮喘等嗜酸性炎症疾病的严重程度，其中 Th2 型细胞因子（IL-4 和 IL-13）和 TGF-β 局部表达，与脂多糖 (LPS) 等细菌因素相关，而不是与过敏原相关。 目的 我们检查了单独使用 IL-4 或 IL-13 或与 LPS 联合刺激的鼻成纤维细胞刺激嗜酸性粒细胞趋化因子的产生，以及其上有 TGF-β(1)。此外，我们还比较了鼻成纤维细胞与肺或皮肤成纤维细胞产生的嗜酸细胞趋化因子的大小。方法从人体活检组织中建立成纤维细胞系。通过RT-PCR评估eotaxin mRNA的表达。通过ELISA测量上清液中嗜酸细胞趋化因子的量。结果IL-4而非IL-13与LPS协同作用以剂量和时间依赖性方式产生嗜酸细胞趋化因子。用IL-4和LPS序贯治疗鼻成纤维细胞没有任何效果。但当 IL-4 和 LPS 添加在一起时，观察到嗜酸细胞趋化因子产生的协同作用。此外，在鼻和皮肤成纤维细胞中观察到这种协同作用，但在肺成纤维细胞中没有观察到。 IL-4 和 LPS 产生的嗜酸性粒细胞趋化因子受到 TGF-β(1) 的调节。 结论 这些结果表明，在鼻息肉病等嗜酸性粒细胞炎症中，IL-4 必须有 LPS 等共刺激物才能强烈诱导嗜酸性粒细胞趋化因子的产生。 TGF-β(1) 的调节可能对嗜酸性炎症的发生具有重要意义。
Background There is growing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. Fibroblasts are a major source of eotaxin. The severity of diseases with eosinophilic inflammation like nasal polyposis, atopic dermatitis and asthma, where Th2-type cytokines (IL-4 and IL-13) and TGF-beta are expressed locally, was shown to correlate with bacterial factors such as lipopolysaccharide (LPS) rather than allergen.Objective We examined eotaxin production by nasal fibroblasts stimulated with IL-4 or IL-13 alone or in combination with LPS, and the effect of TGF-beta(1) on it. Moreover, we compared the magnitude of eotaxin produced by nasal fibroblasts with that produced by lung or skin fibroblasts.Methods Fibroblast lines were established from human biopsy tissue. The expression of eotaxin mRNA was evaluated by RT-PCR. The amount of eotaxin in the supernatants was measured by ELISA.Results IL-4, but not IL-13, synergized with LPS to produce eotaxin in a dose- and time-dependent manner. Sequential treatment of nasal fibroblasts with IL-4 and LPS did not have any effect. But when IL-4 and LPS were added together, synergy for eotaxin production was observed. Moreover, this synergy was observed in nasal and skin fibroblasts, but not in lung fibroblasts. The production of eotaxin by IL-4 and LPS was modulated by TGF-beta(1).Conclusion These results suggest that a co-stimulus like LPS is necessary for IL-4 to make a strong induction of eotaxin in eosinophilic inflammations such as nasal polyposis. Modulation by TGF-beta(1) may have important implications for the development of eosinophilic inflammation.