Interactions of myofibroblasts with airway epithelial cells in allergic airway inflammation

过敏性气道炎症中肌成纤维细胞与气道上皮细胞的相互作用

• 批准号: 14570543
• 负责人: TAKIZAWA Hajime
• 金额: $ 2.24万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570543/
• 关键词: airway remodeling; myofibroblasts; TGFbeta; Th2 cytokines

Asthma is characterized by chronic inflammation of the airway with the presence of Th2 cytokines. Airway remodeling in asthma is, closely related to clinical manifestations. hung myofibroblasts play a critical role,in the airway remodeling and Th2 cytokines may modulate their behavior.Lung fibroblasts were incubated with IL-4 and IL-13 in vitro. Differentiation of normal lung fibroblasts to myofibroblasts was characterized by the expression of a-sniooth muscle actin (α-SMA) as well as morphologic and immunohistochemical analysis. We further studied the effect of a Thi cytokine interferonγ(IFN-γ). Fibroblast proliferation was assessed by MTT assay. We also investigated the effect of these cytokines on cyclooxygenase (COX) gene expression and PGE_2 production.IL-4 and IL-13 increased α-SMA expression and myofibroblastic differentiation and, this effect was attenuated by TFW-γ. IL-4 and IL-13 stimulated fibroblast proliferation. These cytokines downregulated the expression of both COX-l and COX-2 genes and decreased the production of PGE_2.IL-4 arid IL-13 induce differentiation of fibroblasts to myofibroblasts. IFN-γ attenuates this response, but dexamethasone fails to influence on differentiation. IL-4 and IL-13 stimulate fibroblast proliferation and this effect is at least partly due to suppressed COX genes expressions and subsequently decreased PGE_2.production. These findings suggest that Th2 cytokines IL-4 and IL-13 directly act on lung fibroblast to induce fibrocjenic responses.

哮喘的特点是气道慢性炎症与Th2细胞因子的存在。哮喘气道重构与临床表现密切相关。悬挂型肌成纤维细胞在气道重塑中起关键作用，Th2细胞因子可能调节其行为。用IL-4和IL-13体外培养肺成纤维细胞。正常肺成纤维细胞向肌成纤维细胞分化的特征是a-滑滑肌肌动蛋白（α-SMA）的表达以及形态学和免疫组织化学分析。我们进一步研究了一种细胞因子干扰素γ(IFN-γ)的作用。MTT法检测成纤维细胞增殖情况。我们还研究了这些细胞因子对环氧合酶（COX）基因表达和PGE_2生成的影响。IL-4和IL-13增加了α-SMA的表达和肌成纤维细胞的分化，但这种作用被TFW-γ减弱。IL-4和IL-13刺激成纤维细胞增殖。这些细胞因子下调cox - 1和COX-2基因的表达，减少PGE_2的产生。IL-4和IL-13诱导成纤维细胞向肌成纤维细胞分化。IFN-γ减弱了这种反应，但地塞米松不能影响分化。IL-4和IL-13刺激成纤维细胞增殖，这种作用至少部分是由于抑制COX基因表达和随后减少pge_2的产生。这些发现提示Th2细胞因子IL-4和IL-13直接作用于肺成纤维细胞诱导成纤维反应。

项目成果

Saito Y, Azuma A, Kudo S, Takizawa H, Sugawara I.: "Long-term inhalation of diesel exhaust affects cytokine expression in murine lung tissues : comparison between low-and high-diesel exhaust exposure."Exp Lung Res.. 28(6). 493-506 (2002)

Saito Y、Azuma A、Kudo S、Takizawa H、Sukawara I.：“长期吸入柴油废气影响小鼠肺组织中细胞因子的表达：低和高柴油废气暴露之间的比较。”Exp Lung Res.. 28

Hiramatsu s, Azuma A, Kudoh S, Desaki M, Takizawa H, Sugawara I: "Inhalation of diesel exhaust for three months affects major cytokine expression."Exp Lung Res. 29(8). 607-622 (2003)

Hiramatsu s、Azuma A、Kudoh S、Desaki M、Takizawa H、Sukawara I：“吸入柴油废气三个月会影响主要细胞因子的表达。”Exp Lung Res。

Kohyama T, Liu X, Wen FQ, Zhu Yk, Wang H, Kim HJ, Takizawa H, Cieslinski LB, Bamette MS, Rennard SI: "PDE4 inhibitors attenuate fibroblast chemotaxis and contraction of antive collagen gels"Am J Respir Cell Mol Biol. 26(6). 694-701 (2002)

Kohyama T、Liu X、Wen FQ、Zhu Yk、Wang H、Kim HJ、Takizawa H、Cieslinski LB、Bamette MS、Rennard SI：“PDE4 抑制剂减弱成纤维细胞趋化性和抗胶原凝胶收缩”Am J Respir Cell Mol Biol。

Kohyama T, Liu X, Kim HJ, Kobayashi T, Ertl RF, Wen FQ, Takizawa H, Rennard SI.: "Prostacyclin analogs inhibit fibroblast migration"Am J Physiol Lung Cell Mol Physiol. 283(2). L428-L432 (2002)

Kohyama T、Liu X、Kim HJ、Kobayashi T、Ertl RF、Wen FQ、Takizawa H、Rennard SI.：“前列环素类似物抑制成纤维细胞迁移”Am J Physiol Lung Cell Mol Physiol。

Kohyama T, Liu X, Wen FQ, Zhu YK, Wang.H, Kim HJ, Takizawa H, Cieslinski LB, Barnette MS, Rennard SI.: "PDE4 inhibitors attenuate fibroblast chemotaxis and contraction of native collagen gels."Am J Respir Cell Mol Biol. 26(6). 694-701 (2002)

Kohyama T, Liu X, Wen FQ, Zhu YK, Wang.H, Kim HJ, Takizawa H, Cieslinski LB, Barnette MS, Rennard SI.：“PDE4 抑制剂减弱成纤维细胞趋化性和天然胶原凝胶的收缩。”Am J Respir Cell