他克莫斯抑制單核球細胞分泌異位性皮膚炎相關之細胞激素與趨化激素的表現

Tacrolimus suppresses atopic dermatitis-associated cytokines and chemokines in monocyte

張凱婷(Kai-Ting Chang)

指導教授 ： 洪志興

高雄醫學大學/醫學院/醫學研究所碩士班/碩士(2015年)

https://doi.org/10.6832/KMU.2015.00107

摘要

他克莫斯（Tacrolimus）是一種目前廣泛使用的calcineurin抑制劑，它可以用為治療異位性皮膚炎。但他克莫斯對異位性皮膚炎相關的趨化激素是否有影響仍屬未知，本研究澄清他克莫斯對巨噬細胞衍生趨化激素（macrophage-derived chemokine，MDC/CCL22）、嗜酸粒細胞趨化蛋白（I-309/CCL1）、干擾素γ誘導蛋白10（interferon-γ-inducible protein-10，IP-10/CXCL10） 、腫瘤壞死因子α（tumor necrosis factor-α，TNF-α）及生長相關癌基因α（growth-related oncogene-α，GRO-α/ CXCL1）的影響。首先以他克莫斯對單核球細胞進行前處理，之後再以細菌脂多醣（lipopolysaccharide，LPS）刺激，利用酵素免疫分析法（ELISA）測定MDC、I-309、IP-10、TNF-α、GRO-α的濃度。為確認其調控機制，進行西方墨點分析（Western blot）等研究。結果顯示他克莫斯抑制了這些細胞激素的分泌。另外，他克莫斯可抑制細胞絲裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）中Extracellular signal-related kinase （ERK）的磷酸化（phosphorylation）表現量。所以，他克莫斯可能藉由調控與異位性皮膚相關的細胞激素的表現而影響此疾病的表現。

關鍵字

異位性皮膚炎 ； 巨噬細胞衍生趨化激素 ； 嗜酸粒細胞趨化蛋白 ； 干擾素γ誘導蛋白10 ； 生長相關癌基因α ； 他克莫斯

並列摘要

Calcineurin inhibitors (CNIs) exhibit remarkable efficacy in atopic dermatitis(AD). Tacrolimus, one type of CNI, is prevalently used to treat AD. Cytokines and chemokines such as tumor necrosis factor-α(TNF-α), macrophage-derived chemokine (MDC)/CCL22 and I-309/CCL1, interferon-induced protein 10 (IP-10)/CXCL10, and neutrophil chemoattractant growth-related oncogene-α(GRO-α)/CXCL1 are involved in the pathogenesis of AD. However, whether tacrolimus modulates the expression of AD-associated cytokines and chemokines remains unknown. The intracellular mechanisms of tacrolimus are also unclear. Human monocytic cell line THP-1 cells were pretreated with tacrolimus and stimulated with lipopolysaccharide (LPS). The MDC, I-309, IP-10, GRO-α, and TNF-α concentrations of the cell supernatants were measured using enzyme-linked immunosorbent assay. Intracellular signaling was investigated using the Western blot analysis. Tacrolimus suppressed the expression of MDC, IP-10, I-309, GRO-α, and TNF-α in LPS-stimulated THP-1 cells in a dose- and time-dependent manner. Tacrolimus suppressed the LPS-induced phosphorylation of MAPK-extracellular signal-related kinase (ERK). Tacrolimus suppressed LPS-induced MDC, I-309, IP-10, GRO-α, and TNF-α expressions in monocytes through the MAPK-ERK pathway; thus, tacrolimus may yield therapeutic efficacy by modulating AD-associated cytokines and chemokines.

並列關鍵字

atopic dermatitis ； chemokines ； MDC ； I-309 ； IP-10 ； GRO-α ； monocytes ； Tacrolimus

參考文獻

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