title: The macrolide antibiotic, roxithromycin suppresses IFN-gamma-mediated immunological functions of cultured normal human keratinocytes.
abstract: The effects of the macrolide antibiotic, roxithromycin (RXM) on immunological functions of cultured normal human keratinocytes (NHK) were studied. RXM neither modulated the expression of intercellular adhesion molecule-1 (ICAM-1) and human histocompatibility leukocyte antigen (HLA)-DR nor mobilized intracellular free calcium in NHK that were cultured in medium alone. However, the ICAM-1 and HLA-DR expression induced by cultivation with interferon-gamma (IFN-gamma) was upregulated and suppressed, respectively, by pretreatment of NHK with RXM. Whereas ICAM-1 upregulation was observed with RXM at a concentration as high as 0.1 mM, the inhibition of HLA-DR expression by RXM was virtually dose-dependent at doses ranging from 100 nM to 0.1 mM. Accessory cell function of major histocompatibility complex (MHC) class II-bearing NHK in terms of the T-cell response to staphylococcal enterotoxin B was suppressed by pretreatment of NHK with RXM, indicating the functional consequence of RXM-induced reduction of MHC class II molecules. Furthermore, RXM inhibited IFN-gamma-mediated upregulation of IL-1 alpha secretion by NHK. These results show that RXM suppresses immunological functions of keratinocytes triggered by IFN-gamma and suggest the therapeutic relevance of RXM to T cell-mediated inflammatory skin diseases and T cell malignancies such as atopic dermatitis, psoriasis and cutaneous T cell lymphoma, which can be exacerbated by keratinocytes immunologically modulated by exposure to IFN-gamma.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Wakita
authors.forename: Y
authors.initials: Y
authors.lastname: Tokura
authors.forename: F
authors.initials: F
authors.lastname: Furukawa
authors.forename: M
authors.initials: M
authors.lastname: Takigawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000032:analysis; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D015575:Roxithromycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004768:Enterotoxins; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D018799:Intercellular Adhesion Molecule-1; D015575:Roxithromycin; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; D002118:Calcium