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NF‐κB‐dependent lymphocyte hyperadhesiveness to synovial fibroblasts by hypoxia and reoxygenation: potential role in rheumatoid arthritis
Author(s) -
Han MyungKwan,
Kim JongSuk,
Park ByungHyun,
Kim JungRyul,
Hwang ByungYun,
Lee HakYong,
Song EunKyung,
Yoo WanHee
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0502256
Subject(s) - pyrrolidine dithiocarbamate , hypoxia (environmental) , rheumatoid arthritis , immunology , biology , lymphocyte , synovial membrane , nfkb1 , arthritis , inflammation , medicine , cancer research , nf κb , pharmacology , pathology , chemistry , transcription factor , biochemistry , organic chemistry , oxygen , gene
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‐κB (NF‐κB) 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‐κB 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‐κB. Our data suggest that hypoxia/reoxygenation could be an important target for the development of new, therapeutic strategies in RA.