Kojima Fumiaki, Hioki Yuka, Sumida Miori, Iizuka Yoshiko, Kashiwagi Hitoshi, Eto Kei, Arichi Shiho, Maehana Shotaro, Kubo Makoto, Uchida Haruhito A, Ichikawa Takafumi
Department of Pharmacology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-Ku, Sagamihara, 252-0373, Japan.
Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Minami-Ku, Sagamihara, 252-0373, Japan.
Inflamm Regen. 2025 Jun 6;45(1):18. doi: 10.1186/s41232-025-00385-2.
Psoriasis is a chronic inflammatory disease associated with abnormalities in the immune system. Microsomal prostaglandin E synthase-1 (mPGES-1), a terminal enzyme for prostaglandin (PG) E biosynthesis, is highly expressed in the skin of psoriasis patients. However, the detailed role of mPGES-1 in psoriasis remains unclear. In the present study, we aimed to investigate the role of mPGES-1 in psoriasis-like skin inflammation induced by imiquimod (IMQ), a well-established model of psoriasis.
Psoriasis was induced in mPGES-1-deficient (mPGES-1) and wild-type (WT) mice by administering IMQ for 6 days. Psoriasis was evaluated based on the scores of the macroscopic symptoms, including skin scaling, thickness, and redness, and on the histological features. The skin expression of mPGES-1 was determined by real-time polymerase chain reaction and Western blotting. The impact of mPGES-1 deficiency on T-cell immunity was determined by flow cytometry and γδ T-cell depletion in vivo with anti-T-cell receptor (TCR) γδ antibody.
The inflamed skin of mPGES-1 mice showed severe symptoms after the administration of IMQ. Histological analysis further showed significant exacerbation of psoriasis in mPGES-1 mice. In WT mice, the mPGES-1 expression was highly induced at both mRNA and protein levels in the skin, and PGE increased significantly after IMQ administration, while the PGE production was largely abolished in mPGES-1 mice. These data indicate that mPGES-1 is the main enzyme responsible for PGE production in the skin. Furthermore, the lack of mPGES-1 increased the numbers of IL-17A-producing γδ T cells in the skin with IMQ-induced psoriasis, and γδ T-cell depletion resulted in a reduction of the facilitated psoriasis symptoms under the condition of mPGES-1 deficiency.
Our study results demonstrate that mPGES-1 is the main enzyme responsible for skin PGE production, and that mPGES-1 deficiency facilitates the development of psoriasis by affecting the development of T-cell-mediated immunity. Therefore, mPGES-1 might impact both skin inflammation and T-cell-mediated immunity associated with psoriasis.
银屑病是一种与免疫系统异常相关的慢性炎症性疾病。微粒体前列腺素E合酶-1（mPGES-1）是前列腺素（PG）E生物合成的末端酶，在银屑病患者皮肤中高表达。然而，mPGES-1在银屑病中的具体作用仍不清楚。在本研究中，我们旨在探讨mPGES-1在咪喹莫特（IMQ）诱导的银屑病样皮肤炎症中的作用，IMQ是一种成熟的银屑病模型。
通过给予IMQ 6天，在mPGES-1缺陷（mPGES-1）小鼠和野生型（WT）小鼠中诱导银屑病。根据宏观症状评分（包括皮肤脱屑、厚度和发红）以及组织学特征对银屑病进行评估。通过实时聚合酶链反应和蛋白质印迹法测定皮肤中mPGES-1的表达。通过流式细胞术和体内用抗T细胞受体（TCR）γδ抗体清除γδ T细胞来确定mPGES-1缺陷对T细胞免疫的影响。
给予IMQ后，mPGES-1小鼠的炎症皮肤出现严重症状。组织学分析进一步显示mPGES-1小鼠的银屑病明显加重。在WT小鼠中，皮肤中mPGES-1的表达在mRNA和蛋白质水平均被高度诱导，给予IMQ后PGE显著增加，而在mPGES-1小鼠中PGE的产生基本被消除。这些数据表明mPGES-1是皮肤中负责PGE产生的主要酶。此外，在IMQ诱导的银屑病中，mPGES-1的缺乏增加了皮肤中产生IL-17A的γδ T细胞数量，并且γδ T细胞的清除导致在mPGES-1缺陷条件下银屑病症状的减轻。
我们的研究结果表明，mPGES-１是皮肤中负责PGE产生的主要酶，并且mPGES-1缺陷通过影响T细胞介导的免疫发育促进银屑病的发展。因此，mPGES-1可能影响与银屑病相关的皮肤炎症和T细胞介导的免疫。
