The Macrolide Antibiotic, Roxithromycin Suppresses IFN-γ-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-γ (IFN-γ) 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 0.1mM, the inhibition of HLA-DR expression by RXM was virtually dose-dependent at doses ranging from 100nM to 0.1mM. 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-γ-mediated upregulation of IL-1α secretion by NHK. These results show that RXM suppresses immunological functions of keratinocytes triggered by IFN-γ 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-γ.