Prolactin enhances basal and IL-17-induced CCL20 production by human keratinocytes.
Psoriasis vulgaris is an autoimmune dermatosis with Th17 infiltration. Prolactin (PRL) may participate in the pathogenesis of psoriasis. The chemokine CCL20 recruits Th17 cells, and CCL20 production by epidermal keratinocytes is enhanced in psoriatic lesions. We examined the in vitro effects of PRL on CCL20 production in human keratinocytes. PRL increased basal and IL-17-induced CCL20 secretion, and mRNA expression in keratinocytes. CCL20 production by PRL was suppressed by antisense oligonucleotides against the AP-1 components c-Fos and c-Jun, whereas that by IL-17 was suppressed by antisense NF-kappaB p50 and p65. CCL20 production induced by PRL plus IL-17 was suppressed by antisense c-Fos, c-Jun, p50, and p65. PRL alone increased the transcriptional activity of AP-1, and c-Fos and c-Jun expression; moderately enhanced NF-kappaB activity and IkappaBalpha phosphorylation; and potently increased IL-17-induced NF-kappaB activity. MEK and JNK inhibitors suppressed PRL- or PRL-plus-IL-17-induced CCL20 production and AP-1 activities. MEK inhibitor suppressed PRL-induced c-Fos expression, whereas JNK inhibitor suppressed c-Jun expression. PRL induced ERK and JNK phosphorylation. These results suggest that PRL may enhance basal and IL-17-induced CCL20 production in keratinocytes by AP-1 and NF-kappaB activation, which is partially mediated via MEK/ERK and JNK. PRL may promote Th17 infiltration into psoriatic lesions via CCL20.
Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan. nmk@med.teikyo-u.ac.jp
Naoko
N
Kanda
Sayaka
S
Shibata
Yayoi
Y
Tada
Kiyoko
K
Nashiro
Kunihiko
K
Tamaki
Shinichi
S
Watanabe
D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism*
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D020381:Interleukin-17; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D018808:Transcription Factor AP-1; D011388:Prolactin; D011494:Protein Kinases