Role of Interleukin-6 in Transdifferentiation of Bone Marrow Stem Cells into Salivary Acinar Cells

Interleukin-6在骨髓幹細胞轉分化成唾液線細胞過程中所扮演的角色

林佳詠(Chia-Yung Lin) ； 柯美蘭(Mei-Lan Ko) ； 楊志滿(Chih-Man Yang) ； 陳昭瑜(Chao-Yu Chen) ； 陳易駿(Yi-Jyun Chen) ； 陳敏慧(Min-Huey Chen)

《醫學與健康期刊》 6卷1期 (2017/03) Pp. 23-36

摘要

Objectives. In this study, we investigated how the genes, IL-6 and BMP-6, contribute to transdifferentiation of bone marrow stem cells (BMSCs) into acinar cells (ACs). Methods. Bone marrow stem cells and salivary acinar cells were indirectly co-cultured using double-chamber systems. During co-culture, BMP-6 was added. Transdifferentiation efficiency was measured by amylase activity assay. BMP-6 expression in co-cultured BMSCs and the IL-6 concentration in cultured media were assessed using ELISA. The phosphorylation of STAT3 and the downstream factor of IL-6 signal pathway were observed by western blot. Results. During indirect co-culture, the addition of BMP-6 stimulated BMSCs and increased transdifferentiation from 50% to 80%. The BMP-6 expression in co-cultured BMSCs was higher than in individually cultured BMSCs. The cultured medium of ACs had the highest IL-6 concentration, compared to co-cultured media. By adding BMP-6, IL-6 concentration further decreased. Individually cultured BMSCs showed STAT3 expression but indistinct phosphorylation. However, there was clear phosphorylation of STAT3 in co-cultured BMSCs. Conclusion. Many studies report IL-6 and CEBPB induce the expression of BMP-6. We found BMP-6 to be crucial to the promotion of transdifferentiation. This finding combined with the results of IL-6 concentration in cultured media suggest that a BMP-6/IL-6 loop plays an important role in this process. Moreover, phosphorylated STAT3 in co-cultured BMSCs was clearly observed but not in individually cultured BMSCs.

關鍵字

Bone marrow stem cells ； Salivary acinar cells ； Transdifferentiation ； BMP-6/IL-6 loop

並列摘要

目的:研究interleukin-6 (IL-6)及bone morphogenetic protein (BMP-6)在骨髓幹細胞轉分化為分泌澱粉酶之唾液腺細胞過程中扮演的角色。方法:將骨髓幹細胞與頷下腺細胞在進行間接共同培養過程中，利用由外添加BMP-6來其中之骨髓幹細胞，檢驗其轉分化效率，以ELISA觀察骨髓幹細胞中BMP-6的表現量與培養液中IL-6的濃度;以西方墨點法觀察IL-6下游轉錄因子STAT3的磷酸化情形。結果:以適當濃度BMP-6同時刺激，可讓骨髓幹細胞轉分化成唾液腺細胞比例提高到80%。經共同培養之骨髓細胞中BMP-6的表現量較單獨培養者高，而培養液中IL-6的濃度以唾腺細胞培養液最高，共同培養之培養液中濃度反而較低，在外加BMP-6培養的情況下，有更下降的現象。單獨培養的骨髓幹細胞雖有STAT3的表現，但其磷酸化不明顯，而經共同培養的骨髓細胞，則可清楚看到磷酸化STAT3。結論:許多文獻指出BMP-6的表現可被交匯基因IL-6與CEBPB所引導，我們的結果也證實BMP-6是此轉分化現象的關鍵性因素。結合IL-6的濃度結果，BMP-6/IL-6迴圈很可能在此轉分化過程中產一席之地，且也只有經共同培養之骨髓細胞，IL-6下游之STAT3有被磷酸化。

並列關鍵字

骨髓幹細胞 ； 唾液腺細胞 ； 轉分化 ； BMP-6/IL-6迴圈

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