促發炎細胞激素藉由細胞自噬作用調節人類骨髓間質幹細胞之黏附因子表現量

Pro-inflammatory Cytokines Regulate Adhesion Molecules of Human Bone Marrow-derived Mesenchymal Stem Cells via Autophagic Degradation

翁琬婷(Wan-Ting. Weng)

指導教授 ： 伍焜玉

國立清華大學/生命科學院/生物科技研究所/碩士(2018年)

摘要

促發炎細胞激素(Pro-inflammatory cytokines)能夠透過活化細胞自噬作用(autophagy)，促使人類骨髓間質幹細胞(human bone marrow-derived mesenchymal stem cells, BM-MSCs)的表面黏附因子(adhesion molecules)、細胞間隙黏附因子(intercellular adhesion molecule-1, ICAM-1)與血管細胞黏附因子(vascular cell adhesion molecule-1, VCAM-1)之蛋白質表現量上升。為了驗證促發炎細胞激素白介素-1β(interleukin-1β, IL-1β)與腫瘤壞死因子(tumor necrosis factor-α, TNFα)能否透過調控細胞自噬作用進而誘導BM-MSCs的ICAM-1與VCAM-1表現量上升，因此使用了具有降低溶酶體水解酶(lysosomal acid hydrolases)活性的巴佛洛黴素(bafilomycin A, Baf)以及能夠抑制自噬體(autophagosomes)形成的3-MA (3-methyladenine)進行實驗。實驗結果顯示Baf可促進由IL-1β與TNFα所引發的ICAM-1與VCAM-1表現量，使得ICAM-1與VCAM-1的總體表現量趨升；而3-MA則具有相反的作用，使得ICAM-1與VCAM-1的總體表現量下降。由以上實驗結果可得知，BM-MSCs能夠藉由活化細胞自噬作用以調節促發炎細胞激素所引發的ICAM-1和VCAM-1蛋白質表現量。

關鍵字

人類骨髓間質幹細胞 ； 促發炎細胞激素 ； 細胞間隙黏附因子 ； 血管細胞黏附因子 ； 細胞自噬作用

並列摘要

Pro-inflammatory cytokines induce expression of surface adhesion molecules ICAM-1 and VCAM-1 of human bone marrow-derived mesenchymal stem cells (BM-MSCs). To determine whether autophagy plays a role in regulating interleukin-1β (IL-1β)- or tumor necrosis factor-α (TNFα)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), I treated BM-MSCs with bafilomycin A (Baf) which inhibits lysosomal acid hydrolases or with 3-methyladenine (3-MA) which inhibits autophagosome formation. The results reveal that Baf enhanced the expression of ICAM-1 and VCAM-1, while 3-MA inhibited IL-1β- or TNFα-induced expression of ICAM-1 and VCAM-1. These findings suggest that pro-inflammatory cytokine-induced ICAM-1 and VCAM-1 expression in BM-MSCs is regulated by autophagic activation.

並列關鍵字

BM-MSCs ； pro-inflammatory cytokines ； ICAM-1 ； VCAM-1 ； autophagy

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