NF-kappaB-dependent lymphocyte hyperadhesiveness to synovial fibroblasts by hypoxia and reoxygenation: potential role in rheumatoid arthritis.

Abstract

Hypoxia/reoxygenation has been incriminated as a major factor in the pathogenesis of ischemia/reperfusion injury in various ischemic diseases such as rheumatoid arthritis (RA). In this study, we have investigated the effect of hypoxia/reoxygenation on the expression of intercellular adhesion molecule-1 (ICAM-1) in synovial fibroblasts and adherence of lymphocytes to synovial fibroblasts. Hypoxia/reoxygenation strongly activated nuclear factor-kappaB (NF-kappaB) in synovial fibroblasts to the levels produced by phorbol 12-myristate 13-acetate and caused lymphocyte hyperadhesiveness to synovial fibroblasts as well as up-regulation of ICAM-1, both of which were completely blocked by a NF-kappaB antagonist (pyrrolidine dithiocarbamate). These results indicate that hypoxia/reoxygenation has a major role in sequestration of inflammatory cells to synovium mediated by the activation of NF-kappaB. Our data suggest that hypoxia/reoxygenation could be an important target for the development of new, therapeutic strategies in RA.

• Authors: Myung-Kwan Han, Jong-Suk Kim, Byung-Hyun Park, Jung-Ryul Kim, Byung-Yun Hwang, Hak-Yong Lee, Eun-Kyung Song, Wan-Hee Yoo
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 73 Issue 4 Pg. 525-9 (Apr 2003) ISSN: 0741-5400 [Print] England
• PMID: 12660227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Carcinogens
• DNA Primers
• NF-kappa B
• Pyrrolidines
• RNA, Messenger
• Thiocarbamates
• Intercellular Adhesion Molecule-1
• pyrrolidine dithiocarbamic acid
• Tetradecanoylphorbol Acetate
• Oxygen

Topics

• Antioxidants (pharmacology)
• Arthritis, Rheumatoid (metabolism)
• Blotting, Western
• Carcinogens (pharmacology)
• Cell Adhesion (physiology)
• Cells, Cultured
• DNA Primers (chemistry)
• Fibroblasts (metabolism)
• Flow Cytometry
• Humans
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Lymphocytes (metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Oxygen (metabolism)
• Pyrrolidines (pharmacology)
• RNA, Messenger (metabolism)
• Reperfusion Injury (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Synovial Membrane (cytology)
• Tetradecanoylphorbol Acetate (pharmacology)
• Thiocarbamates (pharmacology)
• Up-Regulation