Antimycotics suppress the M alassezia extract‐induced production of CXC chemokine ligand 10 in human keratinocytes

Malassezia , a lipophilic yeast, exacerbates atopic dermatitis. Malassezia products can penetrate the disintegrated stratum corneum and encounter subcorneal keratinocytes in the skin of atopic dermatitis patients. Type 1 helper T ( T h1) cells infiltrate chronic lesions with atopic dermatitis, and antimycotic agents improve its symptoms. We aimed to identify M alassezia ‐induced chemokines in keratinocytes and examine whether antimycotics suppressed this induction. Normal human keratinocytes were incubated with a M alassezia restricta extract and antimycotics. Chemokine expression was analyzed by enzyme‐linked immunosorbent assays and real‐time polymerase chain reaction. Signal transducer and activator of transcription ( STAT )1 activity was examined by luciferase assays. The tyrosine‐phosphorylation of STAT1 was analyzed by western blotting. The M . restricta extract increased the m RNA and protein expression of T h1‐attracting CXC chemokine ligand ( CXCL )10 and STAT 1 activity and phosphorylation in keratinocytes, which was suppressed by a Janus kinase inhibitor. The antimycotics itraconazole, ketoconazole, luliconazole, terbinafine, butenafine and amorolfine suppressed M . restricta extract‐induced CXCL 10 m RNA and protein expression and STAT 1 activity and phosphorylation. These effects were similarly induced by 15‐deoxy‐Δ‐ 12,14 ‐prostaglandin J 2 (15d‐ PGJ 2 ), a prostaglandin D 2 metabolite. Antimycotics increased the release of 15d‐ PGJ 2 from keratinocytes. The antimycotic‐induced suppression of CXCL 10 production and STAT 1 activity was counteracted by a lipocalin‐type prostaglandin D synthase inhibitor. The antimycotics itraconazole, ketoconazole, luliconazole, terbinafine, butenafine and amorolfine may suppress the M . restricta ‐induced production of CXCL 10 by inhibiting STAT 1 through an increase in 15d‐ PGJ 2 production in keratinocytes. These antimycotics may block the T h1‐mediated inflammation triggered by M alassezia in the chronic phase of atopic dermatitis.