Son Yonsu, Ito Tomoki, Ozaki Yoshio, Tanijiri Tsutomu, Yokoi Takashi, Nakamura Kengo, Takebayashi Masashi, Amakawa Ryuichi, Fukuhara Shirou
The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Immunology. 2006 Sep;119(1):36-42. doi: 10.1111/j.1365-2567.2006.02402.x. Epub 2006 Jun 6.
Prostaglandin E2 (PGE2), a major lipid derived from the metabolism of arachidonic acid, is an environmentally bioactive substance produced by inflammatory processes and acts as a cAMP up-regulator that plays an important role in immune responses. It has been reported that PGE2 has the ability to inhibit the production of interleukin-12 by myeloid dendritic cells (MDCs) and macrophages, and then induce preferential T helper type 2 (Th2) cell responses. However, little is known of the function of PGE2 for plasmacytoid dendritic cells (PDCs), which may contribute to the innate and adaptive immune response to viral infection, allergy and autoimmune diseases. In the present study, we compared the biological effect of PGE2 on human PDCs and MDCs. PGE2 caused the death of PDCs but MDCs survived. Furthermore, we found that, whereas PGE2 inhibited interferon-alpha production by PDCs in response to virus or cytosine-phosphate-guanosine, it inhibited interleukin-12 production by MDCs in response to lipopolysaccharide (LPS) or poly(I:C). Although both virus-stimulated PDCs and LPS-stimulated MDCs preferentially induced the development of interferon-gamma-producing Th1 cells, pretreatment with PGE2 led both DC subsets to attenuate their Th1-inducing capacity. These findings suggest that PGE2 represents a negative regulator on not only MDCs but also PDCs.
前列腺素E2（PGE2）是一种由花生四烯酸代谢产生的主要脂质，是炎症过程产生的一种具有环境生物活性的物质，作为一种环磷酸腺苷（cAMP）上调因子，在免疫反应中发挥重要作用。据报道，PGE2能够抑制髓样树突状细胞（MDCs）和巨噬细胞产生白细胞介素-12，进而诱导优先的2型辅助性T细胞（Th2）反应。然而，对于浆细胞样树突状细胞（PDCs）中PGE2的功能知之甚少，而浆细胞样树突状细胞可能有助于对病毒感染、过敏和自身免疫性疾病的先天性和适应性免疫反应。在本研究中，我们比较了PGE2对人PDCs和MDCs的生物学效应。PGE2导致PDCs死亡，但MDCs存活。此外，我们发现，虽然PGE2抑制PDCs对病毒或胞嘧啶-磷酸-鸟苷的反应产生α干扰素，但它抑制MDCs对脂多糖（LPS）或聚肌苷酸-聚胞苷酸（poly(I:C)）的反应产生白细胞介素-12。尽管病毒刺激的PDCs和LPS刺激的MDCs都优先诱导产生γ干扰素的Th1细胞的发育，但用PGE2预处理导致这两种树突状细胞亚群减弱其诱导Th1的能力。这些发现表明，PGE2不仅是MDCs的负调节因子，也是PDCs的负调节因子。
