探討15-keto-PGE2於人類巨噬細胞中對介白素10的影響

第2型糖尿病現今已成為威脅全人類健康的一種疾病，目前第2型糖尿病已被廣泛的認為與肥胖所導致的輕微慢性發炎有關，此種發炎的特徵在於脂肪組織中出現大量巨噬細胞及其所分泌的炎症性細胞激素。介白素10是一種多功能性的細胞激素，可借由抑制炎症性的細胞激素來調控免疫及發炎反應，在脂肪組織中的巨噬細胞所釋放的介白素10可結抗發炎反應，並且保護脂肪細胞免於傷害。在本篇研究中，藉由PMA所誘導分化的人類巨噬細胞，吾人發現15-keto-PGE2 可誘使抗發炎的介白素10之生成，但不會誘使發炎反應的細胞激素生成。而15-keto-PGE2主要是藉由PI3K/AKT/GSK-3β的訊息傳遞途徑來誘使介白素10之生成。15-keto-PGE2 可藉由增強轉錄因子CREB及Sp1對於介白素10 promoter的結合能力來調控介白素10，除此之外，15-keto-PGE2 也經由過氧化氫受體γ之途徑來調控介白素10。綜合以上，這些結果開拓了15-keto-PGE2於調控抗發炎上之重要角色，以及增強了前列腺素代謝反應在免疫反應調控上之重要性。

關鍵字

第2型糖尿病；介白素10 ； 15-keto-PGE2 ；巨噬細胞；過氧化氫受體γ

並列摘要

Type 2 diabetes (T2D) mellitus is currently one of the main health treats for humans. It is now broadly accepted that low-grade chronic inflammation associated with obesity leads to the onset of type 2 diabetes. Obesity-associated inflammation is characterized by an increased abundance of macrophages in adipose tissue along with the production of inflammatory cytokines. Interleuikin-10 (IL-10) is a pleiotropic cytokine that mediate immune and inflammatory responses by inhibiting the synthesis of pro-inflammatory cytokines. IL-10 secreted from macrophages in adipose tissue may counteract the inflammatory effects and protect adipose tissue from injuring. In this study, by using PMA-differentiated THP-1 macrophages, we demonstrated that 15-keto-PGE2 could induce the anti-inflammatory cytokine IL-10 production, but not the pro-inflammatory cytokines (TNF-α, IL-6 and IL-12). The capacity of 15-keto-PGE2 to elevate IL-10 expression level was mediated through PI3K/AKT/GSK-3β signaling pathway. 15-keto-PGE regulated IL-10 promoter activation by increasing the binding activities of transcription factors, CREB and Sp1. Furthermore, 15-keto-PGE2 also induced IL-10 production through partial PPARγ-dependent pathway. Taken together, these findings explore the crucial role of 15-keto-PGE2 in anti-inflammatory effect and enforce the importance of PGE2 catabolism in the immune response.

並列關鍵字

15-keto-PGE2 ； Interleukin-10 ； PPARγ ； THP-1 cell ； macrophage

參考文獻

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探討15-keto-PGE2於人類巨噬細胞中對介白素10的影響

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