Role of heme oxygenase-1 in inflammatory response induced by mechanical stretch in synovial cells

Masanobu Takao, Toshinori Okinaga, Wataru Ariyoshi, Kenjiro Iwanaga, Ikuo Nakamichi, Izumi Yoshioka, Kazuhiro Tominaga, Tatsuji Nishihara

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Objective: The purpose of this study was to investigate the mechanism by which heme oxygenase-1 (HO-1) regulates inflammatory responses induced by mechanical stretch in human fibroblast-like synoviocyte (HFLS) cells. Materials and methods: HFLS cells were cultured in the presence of hemin and seeded into fibronectin-coated silicon chambers. The chambers were attached to a stretching apparatus which applied a uniaxial sinusoidal stretching force. The genetic expressions of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β) and HO-1 were analyzed using real-time RT-PCR. The expression and localization of HO-1 protein were detected by immunofluorescence staining. The amounts of prostaglandin E 2 (PGE 2) released into the culture medium were determined using ELISA. Results: Mechanical stretch enhanced the expressions of COX-2 and IL-1β, and the amount of PGE 2 synthesis in HFLS cells, whereas that of HO-1 was slightly increased. In contrast, treatment with hemin enhanced HO-1 gene expression and mechanical stretch enhanced this expression in hemin-pretreated cells. In addition, hemin pretreatment suppressed PGE 2 synthesis induced by mechanical stretch. Conclusion: We found that constitutive HO-1 expression in hemin-pretreated HFLS cells suppressed mechanical stretch-induced inflammatory responses, suggesting that HO-1 may play a role as a regulation factor in synovial tissue inflammation.

Original languageEnglish
Pages (from-to)861-867
Number of pages7
JournalInflammation Research
Issue number9
Publication statusPublished - 2011 Sep
Externally publishedYes


  • COX-2
  • HO-1
  • IL-1β
  • Mechanical stretch
  • PGE
  • Synovial cell

ASJC Scopus subject areas

  • Immunology
  • Pharmacology


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