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

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. 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-1 beta (IL-1 beta) 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. Mechanical stretch enhanced the expressions of COX-2 and IL-1 beta, 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. 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.