title: IL-18-induced expression of intercellular adhesion molecule-1 in human monocytes: involvement in IL-12 and IFN-gamma production in PBMC.
abstract: IL-18 time- and concentration-dependently upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) in a monocyte population in human PBMC as determined by FACS analysis while the expression of CD11a, CD18, CD29, CD44, and CD62L in monocytes and that of ICAM-1, CD11a, CD18, CD29, CD44, and CD62L in T cells was not influenced by IL-18. IL-18 in the same concentration range stimulated the production of IL-12, TNF-alpha, and IFN-gamma in culture of PBMC; however, IL-18-induced expression of ICAM-1 in monocytes was not inhibited by anti-IL-12, anti-TNF-alpha, or anti-IFN-gamma Ab, suggesting the independence of the upregulating effect of IL-18 on endogenous IL-12, TNF-alpha, and IFN-gamma production. IL-18 also induced the aggregation of PBMC, which was prevented by anti-ICAM-1 and anti-LFA-1 Abs. On the other hand, anti-ICAM-1 and anti-LFA-1 Abs inhibited IL-18-induced production of three cytokines, IL-12, IFN-gamma, and TNF-alpha, by 60 and 40%, respectively. These results strongly suggested that the IL-18-induced upregulation of ICAM-1 and the subsequent adhesive interaction through ICAM-1 on monocytes and LFA-1 on T/NK cells generate an additional stimulatory signaling as well as an efficient paracrine environment for the IL-18-initiated cytokine cascade.
authors.affiliation: Department of Tumour Biology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: H K
authors.initials: HK
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Nishibori
authors.forename: H
authors.initials: H
authors.lastname: Iwagaki
authors.forename: T
authors.initials: T
authors.lastname: Yoshino
authors.forename: T
authors.initials: T
authors.lastname: Morichika
authors.forename: M
authors.initials: M
authors.lastname: Yokoyama
authors.forename: E
authors.initials: E
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Akagi
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002449:Cell Aggregation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000494:pharmacology*; D053727:Interleukin-18 Receptor alpha Subunit; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000187:drug effects / Q000502:physiology; D053724:Receptors, Interleukin-18; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D016169:Lymphocyte Function-Associated Antigen-1; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma