Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Ann Allergy Asthma Immunol. 2010 Jan;104(1):66-72. doi: 10.1016/j.anai.2009.11.003.
Eotaxin-2/CCL24 and eotaxin-3/CCL26 play an important role in eosinophil chemotaxis and activation in asthma. We previously demonstrated that eotaxin/CCL11 is profibrogenic for human lung fibroblasts. The effect of eotaxin-2/ CCL24 and eotaxin-3/CCL26 on lung fibroblasts has not yet been investigated.
To evaluate whether eotaxin-2/CCL24 and eotaxin-3/CCL26 modulate fibrotic properties of lung fibroblasts.
Fibroblast proliferation was evaluated by means of 3-hydroxythymidine incorporation. Collagen production was assessed by means of 3-hydroxyproline incorporation and biochemical staining. Chemotaxis was determined using Boyden chambers. Expression of alpha-smooth muscle actin was evaluated by means of immunostaining. Transforming growth factor beta1 release was assessed using enzyme-linked immunosorbent assay. Parametric analysis of variance, followed by the Tukey-Kramer multiple comparisons test, was used to calculate statistical significance.
Eotaxin-2/CCL24 but not eotaxin-3/CCL26 stimulated human lung fibroblast proliferation and collagen synthesis. In contrast, eotaxin-3/CCL26 but not eotaxin-2/CCL24 promoted fibroblast migration. Neither eotaxin-2/CCL24 nor eotaxin-3/ CCL26 induced the expression of alpha-smooth muscle actin or transforming growth factor beta1 from lung fibroblasts.
Eotaxin-2/CCL24 and eotaxin-3/CCL26 have differential profibrogenic effects on human lung fibroblasts. These CC chemokines may, therefore, contribute to airway remodeling in asthma.
嗜酸性粒细胞趋化因子-2/CCL24 和嗜酸性粒细胞趋化因子-3/CCL26 在哮喘中嗜酸性粒细胞的趋化和激活中发挥重要作用。我们之前证明，嗜酸性粒细胞趋化因子/CCL11 对人肺成纤维细胞具有促纤维化作用。然而，嗜酸性粒细胞趋化因子-2/CCL24 和嗜酸性粒细胞趋化因子-3/CCL26 对肺成纤维细胞的影响尚未得到研究。
评估嗜酸性粒细胞趋化因子-2/CCL24 和嗜酸性粒细胞趋化因子-3/CCL26 是否调节肺成纤维细胞的纤维化特性。
通过 3-羟甲基胸腺嘧啶核苷掺入来评估成纤维细胞增殖。通过 3-羟脯氨酸掺入和生化染色评估胶原产生。通过 Boyden 室测定趋化性。通过免疫染色评估α-平滑肌肌动蛋白的表达。通过酶联免疫吸附试验评估转化生长因子β1 的释放。采用方差分析和 Tukey-Kramer 多重比较检验进行参数分析，以计算统计学意义。
嗜酸性粒细胞趋化因子-2/CCL24 但不是嗜酸性粒细胞趋化因子-3/CCL26 刺激人肺成纤维细胞增殖和胶原合成。相比之下，嗜酸性粒细胞趋化因子-3/CCL26 但不是嗜酸性粒细胞趋化因子-2/CCL24 促进成纤维细胞迁移。嗜酸性粒细胞趋化因子-2/CCL24 和嗜酸性粒细胞趋化因子-3/CCL26 均未诱导肺成纤维细胞表达α-平滑肌肌动蛋白或转化生长因子β1。
嗜酸性粒细胞趋化因子-2/CCL24 和嗜酸性粒细胞趋化因子-3/CCL26 对人肺成纤维细胞具有不同的促纤维化作用。因此，这些 CC 趋化因子可能有助于哮喘中的气道重塑。
