title: 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.affiliation: Department of Microbiology, Chonbuk National University Medical School, Chonju, Korea.
authors.forename: Myung-Kwan
authors.initials: MK
authors.lastname: Han
authors.forename: Jong-Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.forename: Byung-Yun
authors.initials: BY
authors.lastname: Hwang
authors.forename: Hak-Yong
authors.initials: HY
authors.lastname: Lee
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Song
authors.forename: Wan-Hee
authors.initials: WH
authors.lastname: Yoo
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D017931:DNA Primers; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D018799:Intercellular Adhesion Molecule-1; C020972:pyrrolidine dithiocarbamic acid; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen