title: 15-hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid arthritis fibroblast-like synoviocytes.
abstract: 15-Hydroxyprostaglandin dehydrogenase (HPGD) is the key enzyme responsible for the metabolic inactivation of prostaglandin E2 (PGE2) catabolism. PGE2 is one of the predominant catabolic factors involved in rheumatoid arthritis (RA). However, the expression and regulation of HPGD in RA fibroblast‑like synoviocyte (FLS) remain to be elucidated. Disease‑modifying anti‑rheumatic drugs (DMARDs) are the most important anti‑arthritic drugs, which reduce the effect of joint injury. The aim of the present study was to assess the expression of HPGD in RA tissues and cells, and normal synovial tissues and cells. The effect of the most popular DMARDs, hydroxychloroquine, on the expression of HPGD in RA‑FLS was also investigated. Western blotting and immunohistochemical analysis demonstrated that the expression levels of HPGD in human synovium were lower in RA synovium compared with the normal and OA synovium. In RA‑FLS, the expression of HPGD was increased following treatment with several DMARDs, including sulfasalazine, methotrexate, and hydroxychloroquine. Hydroxychloroquine (10 µM) treatment induced the phosphorylation of ERK, SAPK/JNK and p38. Hydroxychloroquine induced a decrease in the release of PGE2, which was restored by mitogen‑activated protein (MAP) kinase pathway inhibitors. Hydroxychloroquine may therefore, affect the pathogenesis of RA through the MAP kinase pathway by regulating the expression of HPGD.
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Choongcheongnam-do 330-930, Republic of Korea.
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Choongcheongnam-do 330-930, Republic of Korea.
authors.forename: Sora
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Choongcheongnam-do 330-930, Republic of Korea.
authors.forename: Haw-Yong
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Choongcheongnam-do 330-930, Republic of Korea.
authors.forename: Hansol
authors.initials: H
authors.lastname: Won
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Choongcheongnam-do 330-930, Republic of Korea.
authors.forename: Sung-Hae
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Choongcheongnam-do 330-930, Republic of Korea.
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Nah
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D006886:Hydroxychloroquine; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D020928:Mitogen-Activated Protein Kinases