Open Access

15-Hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid arthritis fibroblast-like synoviocytes

  • Authors:
    • Hak‑Jae Kim
    • Sora Lee
    • Haw‑Yong Lee
    • Hansol Won
    • Sung‑Hae Chang
    • Seong‑Su Nah
  • View Affiliations

  • Published online on: June 15, 2015     https://doi.org/10.3892/mmr.2015.3931
  • Pages: 4141-4148
  • Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.
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September-2015
Volume 12 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Kim HJ, Lee S, Lee HY, Won H, Chang SH and Nah SS: 15-Hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid arthritis fibroblast-like synoviocytes. Mol Med Rep 12: 4141-4148, 2015
APA
Kim, H., Lee, S., Lee, H., Won, H., Chang, S., & Nah, S. (2015). 15-Hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid arthritis fibroblast-like synoviocytes. Molecular Medicine Reports, 12, 4141-4148. https://doi.org/10.3892/mmr.2015.3931
MLA
Kim, H., Lee, S., Lee, H., Won, H., Chang, S., Nah, S."15-Hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid arthritis fibroblast-like synoviocytes". Molecular Medicine Reports 12.3 (2015): 4141-4148.
Chicago
Kim, H., Lee, S., Lee, H., Won, H., Chang, S., Nah, S."15-Hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid arthritis fibroblast-like synoviocytes". Molecular Medicine Reports 12, no. 3 (2015): 4141-4148. https://doi.org/10.3892/mmr.2015.3931