15-Deoxy-△12,14-Prostaglandin J2 促进实验诱导的结肠炎的消退。,Frontiers in Immunology

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15-Deoxy-△12,14-Prostaglandin J2 促进实验诱导的结肠炎的消退。
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2021-02-02 , DOI: 10.3389/fimmu.2021.615803
Wonki Kim ₁ , Jeong-Hoon Jang ₁ , Xiancai Zhong ₁ , Hyungseok Seo ₂ , Young-Joon Surh _{1,

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Affiliation

不受控制的巨噬细胞功能导致无法解决肠道炎症，并与炎症性肠病 (IBD) 的发病机制有关。15-脱氧-Δ12,14-前列腺素 J2 (15d-PGJ2) 是炎症过程中由花生四烯酸形成的内源性脂质介质之一，据报道可以终止炎症。然而，15d-PGJ2 对肠道炎症的促消退作用和潜在的分子机制仍然未知。在本研究中，我们检查了 15d-PGJ2 对模拟人类 IBD 的葡聚糖硫酸钠 (DSS) 诱导的小鼠结肠炎的分辨率的影响。负责合成 15d-PGJ2 的前列腺素 D 合酶 (PGDS) 的药理学抑制阻碍了用 DSS 治疗的小鼠结肠粘膜炎症的消退。尤其，腹腔注射 15d-PGJ2 加速了实验诱导的结肠炎的消退。15d-PGJ2处理减少了中性粒细胞和M1巨噬细胞的数量，同时增加了M2巨噬细胞的比例。此外，15d-PGJ2 处理的小鼠表现出表达促炎细胞因子 IL-6 的巨噬细胞比例显着降低，同时在饮用水中施用 2.5% DSS 的小鼠结肠粘膜中 STAT3 磷酸化受到抑制。综上所述，这些发现清楚地表明，15d-PGJ2 是由花生四烯酸通过发炎组织中的环氧合酶 2 和 PGDS 活性内源性产生的，可促进肠结肠炎的消退。同时增加M2巨噬细胞的比例。此外，15d-PGJ2 处理的小鼠表现出表达促炎细胞因子 IL-6 的巨噬细胞比例显着降低，同时在饮用水中施用 2.5% DSS 的小鼠结肠粘膜中 STAT3 磷酸化受到抑制。综上所述，这些发现清楚地表明，15d-PGJ2 是由花生四烯酸通过发炎组织中的环氧合酶 2 和 PGDS 活性内源性产生的，可促进肠结肠炎的消退。同时增加M2巨噬细胞的比例。此外，15d-PGJ2 处理的小鼠表现出表达促炎细胞因子 IL-6 的巨噬细胞比例显着降低，同时在饮用水中施用 2.5% DSS 的小鼠结肠粘膜中 STAT3 磷酸化受到抑制。综上所述，这些发现清楚地表明，15d-PGJ2 是由花生四烯酸通过发炎组织中的环氧合酶 2 和 PGDS 活性内源性产生的，可促进肠结肠炎的消退。

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15-Deoxy-△12,14-Prostaglandin J2 Promotes Resolution of Experimentally Induced Colitis.

Uncontrolled macrophage functions cause failure to resolve gut inflammation and has been implicated in the pathogenesis of inflammatory bowel disease (IBD). 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of endogenous lipid mediators formed from arachidonic acid during the inflammatory process, has been reported to terminate inflammation. However, the pro-resolving effect of 15d-PGJ2 on intestinal inflammation and underlying molecular mechanisms remain largely unknown. In the present study, we examined the effects of 15d-PGJ2 on the resolution of dextran sulfate sodium (DSS)-induced murine colitis that mimics human IBD. Pharmacologic inhibition of prostaglandin D synthase (PGDS) responsible for the synthesis of 15d-PGJ2 hampered resolution of inflammation in the colonic mucosa of mice treated with DSS. Notably, intraperitoneal injection of 15d-PGJ2 accelerated the resolution of experimentally induced colitis. 15d-PGJ2 treatment reduced the number of neutrophils and M1 macrophages, while it increased the proportion of M2 macrophages. Moreover, 15d-PGJ2 treated mice exhibited the significantly reduced proportion of macrophages expressing the pro-inflammatory cytokine, IL-6 with concomitant suppression of STAT3 phosphorylation in the colonic mucosa of mice administered 2.5% DSS in drinking water. Taken together, these findings clearly indicate that 15d-PGJ2, endogenously generated from arachidonic acid by cyclooxygenase-2 and PGDS activities in inflamed tissue, promotes resolution of intestinal colitis.

更新日期：2021-02-02

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