title: Cytokine modulation of interactions between cultured human renal tubular and lymphoid blast cells.
abstract: We examined the in vitro cytokine modulation of the interaction of cultured renal tubular epithelial cells (hKEC) with lymphoid effector cells, including mixed lymphocyte reaction (MLR)-derived blasts, Concanavalin A (Con A)-activated blast, and lymphokine-activated killer (LAK) cells. Blast adhesion to hKEC was augmented by treatment with either interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or MLR supernatant. The augmented adhesion statistically correlated with intercellular adhesion molecule-1 (ICAM-1) upregulation on hKEC cells by the cytokines. Blocking of surface ICAM-1 on hKEC or of lymphocyte-function antigen-1 (LFA-1) on the blasts significantly inhibited adhesion. LFA-1 blocking on LAK or MLR blasts resulted in a significant inhibition in cytotoxic function. TNF-alpha and IL-1 beta treatments on hKEC increased the susceptibility to LAK cytotoxicity, whereas IFN-gamma and MLR supernatant treatment significantly reduced this susceptibility. Absorption of IFN-gamma from the MLR supernatant partially restored the susceptibility of LAK cytotoxicity. The combined data suggest the importance of cytokine regulation of LFA-1/ICAM-1 adhesion molecule in these cellular interactions. Although IFN-gamma augments attachment between hKEC and blastic effector cells, this cytokine endows hKEC with resistance to LAK cytotoxicity. Thus, it is clear that cytokine modulation is a complicated phenomenon involving both adhesion molecule regulation-dependent and independent mechanisms.
authors.affiliation: Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Ishikura
authors.forename: T
authors.initials: T
authors.lastname: Chikaraishi
authors.forename: T
authors.initials: T
authors.lastname: Koyanagi
authors.forename: T
authors.initials: T
authors.lastname: Yoshiki
mesh_terms: D000042:Absorption; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D004847:Epithelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology; D007371:Interferon-gamma / Q000493:pharmacokinetics / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D016169:Lymphocyte Function-Associated Antigen-1 / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma