Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4⁺ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis.
Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4⁺ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis.
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DOI：
10.3390/ijms18122758
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发表时间：
2017-12-19
影响因子：
5.6
通讯作者：
Kawakami M
中科院分区：
文献类型：
--
作者：
Takemiya T;Takeuchi C;Kawakami M
微粒体前列腺素合成酶-1（mPGES-1）是一种可诱导的产生前列腺素E2（PGE 2）的末端酶。在我们之前的研究中，我们研究了mPGES-1在实验性自身免疫性脑脊髓炎（EAE）中观察到的炎症和脱髓鞘中的作用，EAE是一种多发性硬化症的动物模型，使用mPGES-1缺陷（mPGES-1−/−）和野生型（wt）小鼠。我们发现，mPGES-1促进炎症，脱髓鞘和瘫痪，并在炎症灶周围的血管内皮细胞和巨噬细胞和小胶质细胞中诱导。在此，我们研究了白细胞介素-1 β（IL-1β）在炎症存在的EAE脊髓中由mPGES-1刺激的细胞间机制中的作用。我们发现，CD 4阳性（CD 4+）T细胞侵入的区域很广泛，野生型小鼠活化的CD 4 + T细胞中的PGE 2受体EP 1 -4比mPGES-1−/−小鼠中的更易诱导。此外，野生型小鼠中65%和48%的CD 4 + T细胞以及mPGES-1−/−小鼠中44%和27%的CD 4 + T细胞产生IL-1β和IL-1受体1（IL-1 r1）。此外，从活化的CD 4 + T细胞释放白细胞介素-17（IL-17）。因此，mPGES-1通过上调活化的CD 4 + T细胞中IL-1β的自分泌功能刺激CD 4 + T细胞之间的细胞间相互作用，从而释放IL-17以促进EAE小鼠中的轴突和髓鞘损伤。
Microsomal prostaglandin synthetase-1 (mPGES-1) is an inducible terminal enzyme that produces prostaglandin E2 (PGE2). In our previous study, we investigated the role of mPGES-1 in the inflammation and demyelination observed in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, using mPGES-1-deficient (mPGES-1−/−) and wild-type (wt) mice. We found that mPGES-1 facilitated inflammation, demyelination, and paralysis and was induced in vascular endothelial cells and macrophages and microglia around inflammatory foci. Here, we investigated the role of interleukin-1β (IL-1β) in the intercellular mechanism stimulated by mPGES-1 in EAE spinal cords in the presence of inflammation. We found that the area invaded by CD4-positive (CD4+) T cells was extensive, and that PGE2 receptors EP1–4 were more induced in activated CD4+ T cells of wt mice than in those of mPGES-1−/− mice. Moreover, IL-1β and IL-1 receptor 1 (IL-1r1) were produced by 65% and 48% of CD4+ T cells in wt mice and by 44% and 27% of CD4+ T cells in mPGES-1−/− mice. Furthermore, interleukin-17 (IL-17) was released from the activated CD4+ T cells. Therefore, mPGES-1 stimulates an intercellular interaction between CD4+ T cells by upregulating the autocrine function of IL-1β in activated CD4+ T cells, which release IL-17 to facilitate axonal and myelin damage in EAE mice.
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影响因子：
3.8
作者：
Adamik, Juraj;Henkel, Matthew;Ray, Anuradha;Auron, Philip E.;Duerr, Richard;Barrie, Arthur
通讯作者：
Barrie, Arthur
炎性小呼林有助于百日咳毒素诱导的IL-1β合成，中性粒细胞血管内爬行和自身免疫性脑脊髓炎。
影响因子：
6.7
作者：
Dumas A;Amiable N;de Rivero Vaccari JP;Chae JJ;Keane RW;Lacroix S;Vallières L
通讯作者：
Vallières L
缺乏实验性自身免疫性脑脊髓炎的胞质磷脂酶A2α缺陷型小鼠具有抗性。
影响因子：
15.3
作者：
Marusic, S;Leach, MW;Pelker, JW;Azoitei, ML;Uozumi, N;Cui, JQ;Shen, MWH;DeClercq, CM;Miyashiro, JS;Carito, BA;Thakker, P;Simmons, DL;Leonard, JP;Shimizu, T;Clark, JD
通讯作者：
Clark, JD
影响因子：
3.7
作者：
Domingues HS;Mues M;Lassmann H;Wekerle H;Krishnamoorthy G
通讯作者：
Krishnamoorthy G
影响因子：
6.1
作者：
Favrais, Geraldine;Schwendimann, Leslie;Lelievre, Vincent
通讯作者：
Lelievre, Vincent