Cytokine modulation of interactions between cultured human renal tubular and lymphoid blast cells.
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.
Takahashi
C
C
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Ishikura
H
H
Chikaraishi
T
T
Koyanagi
T
T
Yoshiki
T
T
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*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma