Cutting edge: combined treatment of TNF-alpha and IFN-gamma causes redistribution of junctional adhesion molecule in human endothelial cells.
Proinflammatory cytokines such as TNF-alpha and IFN-gamma induce cell adhesion molecules in endothelial cells and promote transmigration of leukocytes across endothelial cells. However, when those two were administered together, leukocyte transmigration paradoxically decreased. We cloned a human and bovine homologue of the junctional adhesion molecule (JAM), a novel molecule at the tight junction, and examined the effects of proinflammatory cytokines on JAM in HUVECs. The combined treatment of TNF-alpha plus IFN-gamma caused a disappearance of JAM from intercellular junctions. However, flow cytometry, cell ELISA, and subcellular fractionation analysis demonstrated that the amount of JAM was not reduced. This suggested that JAM changed its distribution in response to proinflammatory cytokines. This redistribution of JAM might be involved in a decrease in transendothelial migration of leukocytes at inflammatory sites.
Ozaki
H
H
Department of Geriatric Medicine, Graduate School of Medicine, Faculty of Medicine, Kyoto University, Japan.
Ishii
K
K
Horiuchi
H
H
Arai
H
H
Kawamoto
T
T
Okawa
K
K
Iwamatsu
A
A
Kita
T
T
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D004338:Drug Combinations; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma