The role of DCLK1 in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells

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Taipei Medical University Institutional Repository > 醫學院 > 國際醫學研究碩博士學位學程 > 博碩士論文 > Item 987654321/63198

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題名:	The role of DCLK1 in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells
作者:	YULIANI, FARA SILVIA
貢獻者:	國際醫學研究博士學位學程林建煌陳炳常
關鍵詞:	DCLK1;severe asthma;thrombin;IL-8/CXCL8
日期:	2023-01-03
上傳時間:	2023-12-07 09:56:22 (UTC+8)
摘要:	Airway neutrophilia has been linked to the severity of asthma and lack of response to corticosteroids. Thrombin, a multifunctional serine protease that participates in the pathogenesis of asthma, can enhance the secretion of IL-8/CXCL8 as a powerful chemoattractant for neutrophils. DCLK1 (doublecortin-like kinase 1) has been identified as a marker of stem cell in a variety of cancer types. The purpose of this research was to investigate the role of DCLK1 in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. We confirmed in this study that the expression of DCLK1 thrombin, and IL-8/CXCL8 (MIP-2) were upregulated in bronchial tissues patients with severe asthma and ovalbumin (OVA)-challenged mice in immunohistochemistry and immunofluorescence staining. In addition, our in vitro study in human epithelial cell lines, BEAS-2B and A549, showed that siRNA against DCLK1 or DCLK1 inhibitor (LRKK2-IN-1) diminished the release of IL-8/CXCL8 triggered by thrombin, indicating that DCLK1 engages in IL-8/CXCL8 production enhanced by thrombin in lung epithelial cells. Thrombin also activated RhoA and YAP through DCLK1 in A549 cells. U0126 (ERK inhibitor) suppressed thrombin-stimulated the activation of DCLK1, RhoA, and YAP, showing that ERK was the upstream of DCLK1/RhoA/YAP pathway. Moreover, siRNA against DCLK1 inhibited thrombin-stimulated YAP and p65 complex and their binding to κB promoter region of IL-8/CXCL8. All of these results demonstrate the role of DCLK1 in mediating thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. Thrombin induces IL-8/CXCL8 expression through DCLK1-dependent RhoA and YAP pathway. Hence, our results provided new insight into the function of DCLK1 in the induction of IL-8/CXCL8 production by thrombin in human lung epithelial cells. Thrombin-stimulated IL-8/CXCL8 production in asthmatic lungs may require DCLK1, suggesting a new therapeutic approach for severe asthma.
描述:	博士指導教授:林建煌共同指導教授:陳炳常委員:林建煌委員:陳炳常委員:黃聰龍委員:黃偉謙委員:鍾啟禮
資料類型:	thesis
顯示於類別:	[國際醫學研究碩博士學位學程] 博碩士論文

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