转化生长因子-β通过核因子-κβ结合位点刺激气道平滑肌细胞中嗜酸粒细胞趋化因子/CC 趋化因子配体 11 的表达及其启动子活性。

Transforming growth factor-β stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor-κβ in airway smooth muscle cells.

机构信息

First Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.

出版信息

Clin Exp Allergy. 2010 May;40(5):763-71. doi: 10.1111/j.1365-2222.2010.03474.x. Epub 2010 Mar 4.

DOI:10.1111/j.1365-2222.2010.03474.x

PMID:20214667

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3712283/

Abstract

BACKGROUND

Chemokines ligands of CCR3 including eotaxin/CC chemokine ligand 11 (CCL11) may contribute to the pathogenesis of asthma. These chemokines and a growth factor (TGF-beta) may be involved in the process of airway remodelling.

OBJECTIVE

We analysed the effects of TGF-beta on the expression of CCR3 ligands in human airway smooth muscle (HASM) cells and investigated the mechanisms.

METHODS

HASM cells were cultured and treated with TGF-beta and Th2 cytokines IL-4 or IL-13. Expression of mRNA was analysed by real-time PCR. Secretion of CCL11 into the culture medium was analysed by ELISA. Transcriptional regulation of CCL11 was analysed by luciferase assay using CCL11 promoter-luciferase reporter plasmids.

RESULTS

IL-4 or IL-13 significantly up-regulated the expression of mRNAs for CCL11 and CCL26. TGF-beta alone did not increase the expression of chemokine mRNAs, but enhanced the induction of only CCL11 by IL-4 or IL-13 among CCR3 ligands. Activity of the CCL11 promoter was stimulated by IL-4, and this activity was enhanced by TGF-beta. Activation by IL-4 or IL-4 plus TGF-beta was lost by mutation of the binding site for signal transducers and activators of transcription-6 (STAT6) in the promoter. Cooperative activation by IL-4 and TGF-beta was inhibited by mutation of the binding site for nuclear factor-kappaB (NF-kappaB) in the promoter. Pretreatment with an inhibitor of NF-kappaB and glucocorticoid fluticasone propionate significantly inhibited the expression of CCL11 mRNA induced by IL-4 plus TGF-beta, indicating the importance of NF-kappaB in the cooperative activation of CCL11 transcription by TGF-beta and IL-4.

CONCLUSION

These results indicate that Th2 cytokines and TGF-beta may contribute to the pathogenesis of asthma by stimulating expression of CCL11. The transcription factors STAT6 and NF-kappaB may play pivotal roles in this process.

摘要

背景

CCR3 的趋化因子配体，包括嗜酸粒细胞趋化因子/CC 趋化因子配体 11（CCL11），可能有助于哮喘的发病机制。这些趋化因子和生长因子（TGF-β）可能参与气道重塑过程。

目的

我们分析了 TGF-β对人气道平滑肌（HASM）细胞中 CCR3 配体表达的影响，并探讨了其机制。

方法

培养 HASM 细胞并进行 TGF-β和 Th2 细胞因子 IL-4 或 IL-13 的处理。通过实时 PCR 分析 mRNA 的表达。通过 ELISA 分析 CCL11 分泌到培养基中的情况。通过 CCL11 启动子-荧光素酶报告质粒的荧光素酶测定分析 CCL11 的转录调控。

结果

IL-4 或 IL-13 显著上调 CCL11 和 CCL26 的 mRNA 表达。TGF-β 单独不会增加趋化因子 mRNA 的表达，但增强了 IL-4 或 IL-13 诱导的 CCR3 配体中仅 CCL11 的诱导。IL-4 刺激 CCL11 启动子活性，而这种活性在 TGF-β存在下增强。启动子中信号转导和转录激活因子 6（STAT6）结合位点的突变使 IL-4 或 IL-4 加 TGF-β的激活丧失。启动子中核因子-κB（NF-κB）结合位点的突变抑制了 IL-4 和 TGF-β的协同激活。NF-κB 抑制剂和糖皮质激素氟替卡松丙酸酯预处理显著抑制了 IL-4 加 TGF-β诱导的 CCL11 mRNA 的表达，表明 NF-κB 在 TGF-β和 IL-4 协同激活 CCL11 转录中具有重要作用。

结论

这些结果表明，Th2 细胞因子和 TGF-β可能通过刺激 CCL11 的表达促进哮喘的发病机制。转录因子 STAT6 和 NF-κB 可能在这个过程中发挥关键作用。

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转化生长因子-β通过核因子-κβ结合位点刺激气道平滑肌细胞中嗜酸粒细胞趋化因子/CC 趋化因子配体 11 的表达及其启动子活性。

Transforming growth factor-β stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor-κβ in airway smooth muscle cells.

机构信息

First Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.

出版信息

Clin Exp Allergy. 2010 May;40(5):763-71. doi: 10.1111/j.1365-2222.2010.03474.x. Epub 2010 Mar 4.

DOI:10.1111/j.1365-2222.2010.03474.x

PMID:20214667

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3712283/

Abstract

BACKGROUND

OBJECTIVE

We analysed the effects of TGF-beta on the expression of CCR3 ligands in human airway smooth muscle (HASM) cells and investigated the mechanisms.

METHODS

RESULTS

CONCLUSION

摘要

背景

目的

我们分析了 TGF-β对人气道平滑肌（HASM）细胞中 CCR3 配体表达的影响，并探讨了其机制。

方法

结果

结论

这些结果表明，Th2 细胞因子和 TGF-β可能通过刺激 CCL11 的表达促进哮喘的发病机制。转录因子 STAT6 和 NF-κB 可能在这个过程中发挥关键作用。

转化生长因子-β通过核因子-κβ结合位点刺激气道平滑肌细胞中嗜酸粒细胞趋化因子/CC 趋化因子配体 11 的表达及其启动子活性。

Transforming growth factor-β stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor-κβ in airway smooth muscle cells.

机构信息

出版信息

BACKGROUND

OBJECTIVE

METHODS

RESULTS

CONCLUSION

背景

目的

方法

结果

结论

相似文献

引用本文的文献

本文引用的文献

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转化生长因子-β通过核因子-κβ结合位点刺激气道平滑肌细胞中嗜酸粒细胞趋化因子/CC 趋化因子配体 11 的表达及其启动子活性。

Transforming growth factor-β stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor-κβ in airway smooth muscle cells.

机构信息

出版信息

BACKGROUND

OBJECTIVE

METHODS

RESULTS

CONCLUSION

背景

目的

方法

结果

结论