Anti-fungal drug liranaftate suppresses fungal element-promoted production of IL-8 in normal human keratinocytes

Abstract

Dermatophytes reside in the stratum corneum of the epidermis, and one scenario in superficial dermatophytosis is that fungi stimulate keratinocytes to secrete chemokines, thereby attracting inflammatory cells. We investigated the effect of the cytokine/chemokine production of keratinocytes solely stimulated by fungal elements. The fungal elements β-D-glucan and trichophytin from Trichophyton rubrum and Trichophyton mentagrophytes augmented production of IL-8 and IL-1 α of cultured normal human epidermal keratinocytes. It was found that keratinocytes can recognize elements of dermatophytes as a pathogen. Next we examined the effect of liranaftate, a representative Japanese thiocarbamate antifungal agent on the production of IL-8 and IL-1 α. Keratinocytes were incubated with this antifungal drug in the presence of β-glucan or trichophytin. Augmented production of IL-8 was profoundly suppressed by the addition of liranaftate to the culture in a dose-dependent manner. Clinically, liranaftate an antifungal drug with IL-8-decreasing activity may reduce infiltration of neutrophils in the skin and their invasion into the epidermis.