title: IFN-gamma-induced HLA-DR but not ICAM-1 expression on cultured dermal papilla cells is downregulated by TNF-alpha.
abstract: The immune response present in untreated alopecia areata (AA) is characterized by overexpression of ICAM-1 and MHC molecules on dermal papilla cells of affected hair follicles and by a distinct cytokine pattern. After successful treatment with the potent contact allergen diphenylcyclopropenone (DCP), adhesion molecules are downregulated and a reversed pattern of cytokines is expressed. To determine which cytokines may be involved in this process we studied the expression and modulation of ICAM-1 and MHC class I and II molecules on cultured dermal papilla cells. Scalp biopsies were obtained from healthy donors and dermal papillae were isolated. The cells were treated with various cytokines and prostanoids. The surface molecules were labeled with FITC-conjugated antibodies, and the expression levels were quantified by FACScan analysis. Incubation with IFN-gamma led to a time-dependent upregulation of the surface molecules studied. IL-1 beta and TNF-alpha synergistically increased the expression of ICAM-1, but they failed to induce MHC molecules. However, both cytokines significantly reduced the IFN-gamma-induced HLA-DR expression. Pretreatment of cells with the cyclooxygenase inhibitor diclofenac, prostanoids, IL-10 or TGF-beta 1 did not alter the constitutive or IFN-gamma-elicited expression of surface molecules. A neutralizing anti-IL-1 beta-antibody did not affect any cytokine-induced changes. We conclude that with regard to surface molecules we can partly initiate in vitro the situation of AA in vivo. Moreover, our results suggest that TNF-alpha, which is markedly increased under DCP treatment, might be an effector of the therapeutic response in AA.
authors.affiliation: Department of Dermatology, Philipp University, Marburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: König
authors.forename: R
authors.initials: R
authors.lastname: Happle
authors.forename: R
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D000328:Adult; D000506:Alopecia Areata / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D002478:Cells, Cultured; D003521:Cyclopropanes / Q000627:therapeutic use*; D015536:Down-Regulation; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D003521:Cyclopropanes; D006684:HLA-DR Antigens; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; C029402:diphenylcyclopropenone