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Background <p>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<sub>2</sub> 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.</p> Methods <p>Psoriasis was induced in mPGES-1-deficient (mPGES-1<sup>−/−</sup>) and wild-type (WT) mice by administering IMQ for 6&#xa0;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.</p> Results <p>The inflamed skin of mPGES-1<sup>−/−</sup> mice showed severe symptoms after the administration of IMQ. Histological analysis further showed significant exacerbation of psoriasis in mPGES-1<sup>−/−</sup> mice. In WT mice, the mPGES-1 expression was highly induced at both mRNA and protein levels in the skin, and PGE<sub>2</sub> increased significantly after IMQ administration, while the PGE<sub>2</sub> production was largely abolished in mPGES-1<sup>−/−</sup> mice. These data indicate that mPGES-1 is the main enzyme responsible for PGE<sub>2</sub> 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.</p> Conclusions <p>Our study results demonstrate that mPGES-1 is the main enzyme responsible for skin PGE<sub>2</sub> 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.</p>

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Genetic deletion of microsomal prostaglandin E synthase-1 promotes imiquimod-induced psoriasis in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月6日

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  • Fumiaki Kojima,
  • Yuka Hioki,
  • Miori Sumida,
  • Yoshiko Iizuka,
  • Hitoshi Kashiwagi,
  • Kei Eto,
  • Shiho Arichi,
  • Shotaro Maehana,
  • Makoto Kubo,
  • Haruhito A. Uchida,
  • Takafumi Ichikawa

摘要

Background

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) E2 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.

Methods

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.

Results

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 PGE2 increased significantly after IMQ administration, while the PGE2 production was largely abolished in mPGES-1−/− mice. These data indicate that mPGES-1 is the main enzyme responsible for PGE2 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.

Conclusions

Our study results demonstrate that mPGES-1 is the main enzyme responsible for skin PGE2 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.