title: Various cytokines modulate ICAM-1 shedding on melanoma- and CTCL-derived cell lines: inverse regulation of ICAM-1 shedding in a Sézary cell line by interferon-gamma.
abstract: BACKGROUND
  Since soluble intercellular adhesion molecules 1 (sICAM-1) retain their ability to bind to their ligand, they can interfere in cell-mediated immunosurveillance.
  
  
  OBJECTIVE
  We studied the impact of various cytokines on ICAM-1 release of several tumor cell lines.
  
  
  METHODS
  Two melanoma cell lines (M19, M26), 1 B lymphoblastoid cell line (Daudi), 1 erythroleukemia cell line (K562), 1 Sézary-cell-derived cell line (SeAx), 1 cell line derived from a mycosis fungoides lesion (MyLa) and normal peripheral blood mononuclear cells (PBMC) were grown in the presence of interferon gamma (IFN-gamma), IFN-alpha, interleukin-2 (IL-2), IL-6 and tumor necrosis factor alpha (TNF-alpha) in various concentrations. ICAM-1 release into the supernatant was measured after 24 and 48 h using an enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  PBMC and the B lymphoblastoid cell line did not shed detectable amounts of sICAM-1. In all other cell lines, ICAM-1 shedding was found with and without cytokine stimulation. In all cell cell lines except the CTCL-derived one, ICAM-1 shedding was marginally affected by IFN-alpha, IL-2 and IL-6. TNF-alpha and IFN-gamma enhanced the shedding in a time- and dose-dependent manner. In the SeAx line, IL-2 and IFN-gamma inhibited ICAM-1 release. By contrast, TNF-alpha and IL-6 enhanced it. The CTCL-derived MyLa responded to IFN-alpha with a dose-dependent increase in ICAM-1 shedding. All other cytokines had marginal influence.
  
  
  CONCLUSIONS
  Cytokine-modulated ICAM-1 shedding shows quantitative and qualitative differences in the investigated cell lines. This might have implications for the pathophysiology of cutaneous malignancies and their susceptibility to immunotherapies.
authors.affiliation: Department of Dermatology, University of Zurich Medical School, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Dummer
authors.forename: S
authors.initials: S
authors.lastname: Sigg-Zemann
authors.forename: K
authors.initials: K
authors.lastname: Kalthof
authors.forename: S
authors.initials: S
authors.lastname: Muletta
authors.forename: J C
authors.initials: JC
authors.lastname: Meyer
authors.forename: G
authors.initials: G
authors.lastname: Burg
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002464:Cell Migration Inhibition; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009182:Mycosis Fungoides / Q000378:metabolism* / Q000473:pathology; D012751:Sezary Syndrome / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016898:Interferon-alpha; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma