Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa, Ishikari-Tobetsu, Japan.
Immunol Lett. 2011 Dec 30;141(1):55-60. doi: 10.1016/j.imlet.2011.07.005. Epub 2011 Aug 3.
While interleukin (IL)-33, a novel member of the IL-1 family, seems to promote T helper type 2 (Th2)-associated inflammations and allergic diseases, the stimulating factors for IL-33 production are less well characterized. Prostaglandin E(2) (PGE(2)) has been shown to suppress immune cell functions. However, the immune enhancement by this mediator is not well understood. In the present study, we examined the effect of PGE(2) on IL-33 production by dendritic cells (DCs). Bone marrow-derived DCs were stimulated with lipopolysaccharide (LPS) in the presence or absence of PGE(2). LPS increased mRNA expression of the IL-1 family members, IL-1, IL-18, and IL-33 in DCs. PGE(2) alone showed slight effect on IL-1, IL-18, and IL-33 mRNA expression in DCs. Of note, LPS combined with PGE(2) caused in a synergistic enhancement of mRNA expression of IL-33 but not IL-1 and IL-18. In addition, PGE(2) dramatically enhanced IL-33 protein production by DCs upon LPS stimulation. The protein kinase A (PKA) inhibitor H89 significantly inhibited the PGE(2)-mediated enhancement of IL-33 production by DCs. Thus, PGE(2) appears to enhance IL-33 mRNA expression and its protein synthesis via PKA pathway in DCs. PGE(2) may promote Th2-mediated inflammations through the enhancement of IL-33 production by DCs, which might be associated with the pathogenesis of allergic diseases.
白细胞介素 (IL)-33，一种新的 IL-1 家族成员，似乎促进辅助性 T 细胞 2（Th2）相关炎症和过敏性疾病，但产生 IL-33 的刺激因素尚未得到很好的描述。前列腺素 E2 (PGE2) 已被证明可抑制免疫细胞功能。然而，这种介质的免疫增强作用尚不清楚。在本研究中，我们研究了 PGE2 对树突状细胞 (DC) 产生 IL-33 的影响。骨髓来源的 DC 在存在或不存在 PGE2 的情况下用脂多糖 (LPS) 刺激。LPS 增加了 DC 中 IL-1 家族成员 IL-1、IL-18 和 IL-33 的 mRNA 表达。PGE2 单独对 DC 中 IL-1、IL-18 和 IL-33 的 mRNA 表达仅有轻微影响。值得注意的是，LPS 与 PGE2 联合使用可协同增强 IL-33 的 mRNA 表达，但不增强 IL-1 和 IL-18。此外，PGE2 可显著增强 LPS 刺激的 DC 中 IL-33 蛋白的产生。蛋白激酶 A (PKA) 抑制剂 H89 显著抑制 PGE2 介导的 DC 中 IL-33 产生的增强作用。因此，PGE2 似乎通过 PKA 途径增强 DC 中 IL-33 的 mRNA 表达及其蛋白合成。PGE2 可能通过增强 DC 产生 IL-33 来促进 Th2 介导的炎症，这可能与过敏性疾病的发病机制有关。
