Alleviation of collagen-induced arthritis by the benzoxathiole derivative BOT-4-one in mice: Implication of the Th1- and Th17-cell-mediated immune responses

Byung Hak Kim, Bo Ruem Yoon, Eun Kyoung Kim, Kum Hee Noh, Sun Ho Kwon, Eun Hee Yi, Hyun Gyu Lee, Jung Sook Choi, Seong Wook Kang, In Chul Park, Won Woo Lee, Sang Kyu Ye

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Autoimmune rheumatoid arthritis is characterized by chronic inflammation and hyperplasia in the synovial joints. Although the cause of rheumatoid arthritis is largely unknown, substantial evidence has supported the importance of immune cells and inflammatory cytokines in the initiation and progression of this disease. Herein, we demonstrated that the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) alleviated type II collagen-induced arthritis in a mouse model. The levels of pro-inflammatory cytokines are elevated in both human patients with rheumatoid arthritis and mice with collagen-induced arthritis. BOT-4-one treatment reduced the levels of pro-inflammatory cytokines in mice and endotoxin-stimulated macrophages. BOT-4-one treatment suppressed the polarization of Th1- and Th17-cell subsets by inhibiting the expression and production of their lineage-specific master transcription factors and cytokines, as well as activation of signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited mitogen-activated protein kinase and NF-kappaB signaling as well as the transcriptional activities and DNA-binding of transcription factors, including activator protein-1, cAMP response element-binding protein and NF-kappaB. Our results suggest that BOT-4-one may have therapeutic potential for the treatment of chronic inflammation associated with autoimmune rheumatoid arthritis.

Original languageEnglish
Pages (from-to)47-57
Number of pages11
JournalBiochemical Pharmacology
Volume110-111
DOIs
StatePublished - 15 Jun 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.

Keywords

  • 2-Cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one)
  • Mitogen-activated protein kinase (MAPK)
  • NF-kappaB (NF-κB)
  • Rheumatoid arthritis
  • Signal transducer and activator of transcription (STAT)

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