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Production of soluble ICAM-1 from human endothelial cells induced by IL-1β and TNF-α

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Abstract

The present study was designed to establish the effects of cytokines on soluble ICAM-1 (sICAM-1) production by human endothelial cells (EC) and ICAM-1 expression on these cells and the effects of purified sICAM-1 on lympho-cyte-EC adhesion. Expression of ICAM-1 and production of sICAM-1 were measured by a specific ELISA method. ICAM-1 expression was enhanced by IL-1β, TNF-α, and most effectively by IFN-γ. IL-4, IL-6, M-CSF, or GM-CSF showed no effects on ICAM-1 expression. IL-4 (100 units/ml) or IL-6(100 units/ml) abolished the enhancing effect of IL-1β, while TNF-α (1, 10, 100 units/ml) synergized with IL-1β to promote ICAM-1 expression in EC. In contrast with the transient increase of cell-associated ICAM-1 expression after activiation by IL-1β, which peaked 40 h poststimulation and declined thereafter, sICAM-1 continued to accumulate in culture supernatants even after 48 h poststimulation in IL-1β-stimulated EC. IL-1β treatment resulted in an increase in adhesion. sICAM-1, purified from cell-free supernatants obtained after a 48-h culture of EC in IL-1β by affinity chromatography using monoclonal ICAM-1 antibody coupled to Sepharose beads, significantly inhibited lymphocyte EC adhesion. Preincubation of lymphocytes with conditioned medium of EC cultured with 100 units/ml IL-1β for 48 h, which contained a considerable amount of sICAM-1, resulted in a significant inhibition of lymphocyte adhesion to IL-1β-stimulated EC. These results suggest that there is a cumulative increase in sICAM-1 concentration in the vicinity of cytokine-stimulated EC and that this sICAM-1 modulates ICAM-1-mediated cell to cell interaction.

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Authors and Affiliations

  1. Department of Clinical Immunology Medical Institute of Bioregulation, Kyushu University, 874, 69. Beppu, Japan

    Michi Hashimoto, Masao Shingu, Ichiko Ezaki & Masashi Nobunaga

  2. Obstetrics and Gynecology, Beppu National Hospital Beppu, 874-01, Japan

    Makoto Minamihara, Keiji Kato & Hisao Sumioki

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  1. Michi Hashimoto
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  2. Masao Shingu
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  3. Ichiko Ezaki
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  4. Masashi Nobunaga
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  5. Makoto Minamihara
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  6. Keiji Kato
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  7. Hisao Sumioki
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Hashimoto, M., Shingu, M., Ezaki, I. et al. Production of soluble ICAM-1 from human endothelial cells induced by IL-1β and TNF-α. Inflammation 18, 163–173 (1994). https://doi.org/10.1007/BF01534557

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