title: Calcipotriol increases hCAP18 mRNA expression but inhibits extracellular LL37 peptide production in IL-17/IL-22-stimulated normal human epidermal keratinocytes.
abstract: Interleukins (IL)-17A and -22 are involved in the patho-genesis of psoriasis. Cathelicidin LL37 serves as not only antimicrobial peptide but also as autoinflammatory mediator. 1,25-Dihydroxyvitamin D3 analogues, such as calcipotriol, are used as topical treatment for psoriasis. However, the effect of calcipotriol on the mRNA expression/production of human cathelicidin antimicrobial protein (hCAP18) and LL37 peptide by IL-17A/IL-22-stimulated keratinocytes remains controversial. To evaluate the modulatory action of calcipotriol on the production of hCAP18 and LL37, we analysed hCAP18 mRNA expression and hCAP18/LL37 peptide production in IL-17A/IL-22-stimulated cultured human keratinocytes by real-time qPCR, ELISA, western blotting, and immunocytostaining. By western blotting, hCAP18 protein was detected in keratinocytes cultured for 72 h with IL-17/IL-22. Calcipotriol increased hCAP18 mRNA expression in IL-17/IL-22-stimulated keratinocytes. However, LL37 peptide in the culture supernatants was reduced by calcipotriol. Immunostaining revealed that the overproduced LL37 resides within the cells. LL37 promotes psoriasis via interaction with extracellular DNA, but may suppress psoriasis by interfering cytosolic DNA.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. jsakabe@med.uoeh-u.ac.jp, jsakabe@hama-med.ac.jp.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sakabe
authors.forename: Takatsune
authors.initials: T
authors.lastname: Umayahara
authors.forename: Mizuho
authors.initials: M
authors.lastname: Hiroike
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Shimauchi
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ito
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D054804:Cathelicidins / Q000378:metabolism*; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000494:pharmacology*; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D023181:Antimicrobial Cationic Peptides; D002117:Calcitriol; D054804:Cathelicidins; D003879:Dermatologic Agents; D020381:Interleukin-17; D016209:Interleukin-8; D007378:Interleukins; D012333:RNA, Messenger; D000097043:Interleukin-22; C055085:calcipotriene