Histamine induces human lung fibroblast-mediated collagen gel contraction via histamine H1 receptor
Histamine induces human lung fibroblast-mediated collagen gel contraction via histamine H1 receptor
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DOI：
10.3109/01902148.2014.900155
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发表时间：
2014-06-01
影响因子：
1.7
通讯作者：
Kohyama, Tadashi
中科院分区：
文献类型：
--
作者：
Horie, Masafumi;Saito, Akira;Kohyama, Tadashi
背景：气道重塑与难治性哮喘的不可逆气流限制有关，包括平滑肌质量增加和上皮下纤维化。活化的成纤维细胞获得收缩表型，参与组织收缩和细胞外基质的结构改变。组胺是变应性炎症的有效介质，实质上参与哮喘的病理生理。目的：我们推测组胺可能在气道重塑中起作用，并探讨其对成纤维细胞介导的胶原凝胶收缩的影响。方法：研究成纤维细胞介导的胶原凝胶收缩。通过使用特异性组胺受体拮抗剂、IP3受体拮抗剂和PKC抑制剂来表征组胺对胶原凝胶收缩的调节。结果：在4个原代培养的成人肺成纤维细胞和3个胎儿肺成纤维细胞系中，组胺浓度大于10(-6)M时，组胺诱导包埋人肺成纤维细胞的胶原凝胶呈时间依赖性收缩。这种作用被H1受体拮抗剂减弱，而H2 - H4受体拮抗剂则没有表现出抑制作用。此外，IP3受体介导的Ca2+动员与组胺对胶原凝胶收缩的作用有关。结论：我们的研究结果表明，组胺通过对肺成纤维细胞的作用参与气道重塑，抗组胺药物，特别是H1受体拮抗剂，可能对一部分哮喘患者有益。
Background: Airway remodeling is implicated in irreversible airflow limitation of refractory asthma, which includes increased smooth muscle mass and subepithelial fibrosis. Activated fibroblasts acquire contractile phenotype to participate in tissue contraction and structural alteration of extracellular matrices. Histamine is a potent mediator of allergic inflammation, substantially involved in asthmatic pathophysiology. Objective: We hypothesized that histamine might play a role in airway remodeling, and investigated its effect on fibroblast-mediated collagen gel contraction. Methods: Fibroblast-mediated collagen gel contraction was studied. Histamine's regulation of collagen gel contraction was characterized by using specific histamine-receptor antagonists, an IP3 receptor antagonist and a PKC inhibitor. Results: Histamine induced contraction of collagen gels embedded with human lung fibroblasts, in a time-dependent manner, and at the concentration more than 10(-6) M, both in four primary cultured adult lung fibroblasts and three fetal lung fibroblast cell lines. This effect was attenuated by H1 receptor antagonist, whereas those for H2 to H4 receptors failed to show an inhibitory effect. Furthermore, IP3 receptor-mediated Ca2+ mobilization was implicated in histamine's action on collagen gel contraction. Conclusions: Our results suggest that histamine is involved in airway remodeling through its action on lung fibroblasts, and antihistamine drugs, especially H1 receptor antagonists, might be potentially beneficial for a subset of asthmatic patients.