Background: Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that acts downstream of cyclooxygenase and plays a major role in inflammation by converting prostaglandin (PG) H₂to PGE₂. The present study investigated the effect of genetic deletion of mPGES-1 on the development of immunologic responses to experimental colitis induced by dextran sodium sulfate (DSS), a well-established model of inflammatory bowel disease (IBD).Methods: Colitis was induced in mice lacking mPGES-1 (mPGES-1^−/−mice) and wild-type (WT) mice by administering DSS for 7 days. Colitis was assessed by body weight loss, diarrhea, fecal bleeding, and histological features. The colonic expression of mPGES-1 was determined by real-time PCR, western blotting, and immunohistochemistry. The impact of mPGES-1 deficiency on T cell immunity was determined by flow cytometry and T cell depletionin vivo.Results: After administration of DSS, mPGES-1^−/−mice exhibited more severe weight loss, diarrhea, and fecal bleeding than WT mice. Histological analysis further showed significant exacerbation of colonic inflammation in mPGES-1^−/−mice. In WT mice, the colonic expression of mPGES-1 was highly induced on both mRNA and protein levels and colonic PGE₂increased significantly after DSS administration. Additionally, mPGES-1 protein was localized in the colonic mucosal epithelium and infiltrated inflammatory cells in underlying connective tissues and the lamina propria. The abnormalities consistent with colitis in mPGES-1^−/−mice were associated with higher expression of colonic T-helper (Th)17 and Th1 cytokines, including interleukin 17A and interferon-γ. Furthermore, lack of mPGES-1 increased the numbers of Th17 and Th1 cells in the lamina propria mononuclear cells within the colon, even though the number of suppressive regulatory T cells also increased. CD4⁺T cell depletion effectively reduced symptoms of colitis as well as colonic expression of Th17 and Th1 cytokines in mPGES-1^−/−mice, suggesting the requirement of CD4⁺T cells in the exacerbation of DSS-induced colitis under mPGES-1 deficiency.Conclusions: These results demonstrate that mPGES-1 is the main enzyme responsible for colonic PGE₂production and deficiency of mPGES-1 facilitates the development of colitis by affecting the development of colonic T cell–mediated immunity. mPGES-1 might therefore impact both the intestinal inflammation and T cell–mediated immunity associated with IBD.

Microsomal prostaglandin E synthase-1 (mPGES-1) is an isozyme of the prostaglandin (PG) E synthase that acts downstream of cyclooxygenase and catalyzes the conversion of PGH₂ to PGE₂. The impact of genetic deletion of mPGES-1 on the development of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, a well-established model of inflammatory bowel disease (IBD), was investigated in this study. After administration of TNBS, mice deficient in mPGES-1 (mPGES-1^−/− mice) showed more severe colitis than did wild-type (WT) mice. Histological examination revealed that mPGES-1^−/− mice had markedly exacerbated symptoms of colitis. mPGES-1 expression was detectable in the colons of WT mice at both the mRNA and protein levels. Lack of mPGES-1 resulted in marked reduction of colonic PGE₂ production. Our study also showed a significant increase in colonic expression of interleukin-17A (IL-17A), as well as interferon γ (IFNγ) and tumor necrosis factor α, during colitis in mPGES-1^−/− mice compared with that in WT mice. Furthermore, loss of mPGES-1 increased the populations of IL-17A-producing T-helper (Th) 17 and IFNγ-producing Th1 cells in mesenteric lymph nodes. These results suggest that mPGES-1 is the main enzyme responsible for colonic PGE₂ production and deficiency of mPGES-1 facilitates the development of colitis and T-cell-mediated immunity. mPGES-1 might, therefore, impact T-cell-related immune response associated with IBD.

The mobile tmexCD‐toprJ gene clusters encode resistance‐nodulation‐division (RND)‐type multidrug efflux pumps which confer resistance to multiple antimicrobials, including tigecycline. Here we report the first identification of tmexCD‐toprJ‐ harbouring Pseudomonas aeruginosa strain KAM950, isolated from hospital sewage in Japan in 2022. The isolate exhibited reduced susceptibility to tigecycline and carbapenems. Complete genome sequence analysis showed that KAM950 belongs to sequence type 244 (ST244) according to multilocus sequence typing, an internationally recognised epidemic clone, and harbours multiple antimicrobial resistance genes, including the tmexCD‐toprJ variant, tmexC6D6‐toprJ1b . Notably, the tmexC6D6‐toprJ1b gene cluster was located on the chromosome, adjacent to the transcriptional regulator gene tnfxB6 and an IS 5 /IS 1182 family transposase gene. Furthermore, an IS 4 ‐mediated disruption of the porin gene oprD was observed, potentially contributing to carbapenem resistance. BLASTn analysis revealed that the IS 5 /IS 1182‐tnfxB6‐tmexC6D6‐toprJ1b gene cluster present in both chromosomal and plasmid sequences among the order Pseudomonadaceae , indicating potential horizontal gene transfer of tnfxB6‐tmexC6D6‐toprJ1b mediated by IS 5 /IS 1182 . Our findings highlight the ongoing expansion of variant diversity and geographic spread of tmexCD‐toprJ ‐like gene clusters, and underscore the importance of genomic surveillance for emerging antimicrobial resistance determinants in both clinical and environmental settings.

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.