J Korean Rheum Assoc.  2002 Mar;9(1):23-33.

Hypoxia Increases the Expression of ICAM-1 in Cultured Human Synovial Fibroblasts

Affiliations
  • 1Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Chonju, Korea.
  • 2Department of Orthopedic Surgery, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Chonju, Korea.

Abstract


OBJECTIVE
Hypoxic conditions are thought to be exist in inflamed arthritic synovium.Several in vitro and in vivo studies indicate that hypoxia can initiate events that lead to pro-adhesive changes.Therefore,this study was designed to examine the effects of hypoxia on the expression of ICAM-1 by cultured human synovial fibroblasts.
METHODS
Synovial fibroblasts were isolated from patients with RA and cultured at hypoxic condition.To quantify the expression of ICAM-1 mRNA in synovial fibroblasts,RT-PCR was performed.The levels of cytokines in culture supernatants were measured by ELISA.The activation of NF- RESULTS
The expression ICAM-1 mRNA was increased at 12 to 48 hours of hypoxic stimuli and peaked at 24 hours (p < 0.01).The concentration of IL-1 and TNF-alpha was increased as the duration of hypoxic stimuli was increased.Hypoxia also induced activatation of NF- microB,which was inhibited by antioxidant (pyrroli-dine dithiocarbamate). Fibroblast-lymphocyte adhesive interaction was increased significantly by hypoxic stimuli (p < 0.01).
CONCLUSIONS
Synovial hypoxia may have an important role in inflammatory synovitis,in part,as a cause of adhesion molecule (ICAM-1)expression in synovial fibroblasts and recruitment of inflammatory cells.


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