title: Candida albicans abrogates the expression of interferon-gamma-inducible protein-10 in human keratinocytes.
abstract: Candida albicans is the predominant causative agent of human cutaneous candidiasis. Epidermal keratinocytes play an important role in the cutaneous immune response through the production of cytokines and chemokines, including IFN-gamma-inducible protein 10 (IP-10). Here, we investigated the influence of C. albicans infection on IP-10 production by normal human epidermal keratinocytes (NHEK) in vitro. Our results showed that IFN-gamma-stimulated NHEK showed enhanced IP-10 mRNA and protein expression; this expression was downregulated by C. albicans infection. Candida tropicalis also impaired IFN-gamma-induced IP-10 expression, but Candida glabrata did not. Heat-killed C. albicans did not impair IFN-gamma-induced IP-10 expression. We found that coincubation of NHEK with live C. albicans without cell-to-fungi contact impaired IFN-gamma-induced IP-10 mRNA and protein expression in NHEK, suggesting the role of soluble factors derived from live C. albicans in this impairment. Enzyme-linked immunosorbent assay analysis revealed that C. albicans and C. tropicalis could produce marked levels of prostaglandin (PG) E(2), while C. glabrata produced low levels of this prostaglandin. Treatment with E-series prostaglandin receptor antagonists, AH6809 and AH23848, restored IFN-gamma-induced IP-10 expression in C. albicans-infected NHEK. Thus, Candida-derived PGE(2) may impair IFN-gamma-induced IP-10 expression in human keratinocytes and may play a role in the pathogenesis of cutaneous candidiasis.
authors.affiliation: Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Shiraki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: Masataro
authors.initials: M
authors.lastname: Hiruma
authors.forename: Akemi
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Shigaku
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D002176:Candida albicans / Q000472:pathogenicity*; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D054357:Chemokine CXCL10; D012333:RNA, Messenger; D007371:Interferon-gamma; D015232:Dinoprostone