Erratum to "Neutrophil-dominant psoriasis-like skin inflammation induced by epidermal-specific expression of Raf in mice" [J. Dermatol. Sci. 58 (2010) 28-35].
BACKGROUND
Raf is one of the downstream effectors of Ras GTPases. The induction of Raf in the epidermis causes the proliferation of keratinocytes and epidermal hyperplasia. However, skin inflammation accompanying Ras-induced epidermal reactions has not been fully delineated.


OBJECTIVE
The aim of this study was to characterize inflammatory reactions induced by epidermal-specific Raf expression and to elucidate its role in skin inflammation.


METHODS
K14-Raf:ER transgenic mice, in which the 4-hydroxytamoxifen (4OHT)-responsive mutant estrogen receptor (ER) ligand binding domain-Raf fusion gene was expressed under control of the keratin 14 promoter, were used to characterize inflammatory reactions induced by Raf expression in the epidermis.


RESULTS
A single topical application of 4OHT induced the expression of phosphorylated extracellular signal-related kinase 1/2 and elicited neutrophil-dominant inflammatory infiltrates in the skin. The Raf expression also rapidly induced the production of several cytokines and chemokines, including VEGF and CXCL1, by keratinocytes and inmouse skin in vivo. Furthermore, CD4-positive cells from regional lymph nodes had the potential to differentiate into IFNg- and IL17-producing cells. Treatment with an anti-Gr-1 antibody diminished the Raf-induced cutaneous inflammation and partially reversed the epidermal hyperplasia and hyperkeratosis.


CONCLUSIONS
Activation of the Raf signaling pathway is involved in the epidermal hyperplasia and the neutrophil-dominant cutaneous inflammatory reactions which are characteristics of psoriasis.
Tartutani
Masahito
M
Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. tarutani@kochi-u.ac.jp
Imai
Yasutomo
Y
Yasuda
Koubun
K
Tsutsui
Hiroko
H
Nakanishi
Kenji
K
Yamanishi
Kiyofumi
K
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D054360:Chemokine CXCL1 / Q000032:analysis; D004817:Epidermis / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007371:Interferon-gamma / Q000032:analysis; D020381:Interleukin-17 / Q000032:analysis; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000473:pathology*; D011401:Promoter Regions, Genetic; D011565:Psoriasis / Q000209:etiology* / Q000473:pathology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000009:adverse effects / Q000031:analogs & derivatives; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D048490:raf Kinases / Q000378:metabolism*
D015704:CD4 Antigens; D054360:Chemokine CXCL1; D020381:Interleukin-17; D053547:Keratin-14; C507446:Krt14 protein, mouse; D011960:Receptors, Estrogen; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen; C016601:afimoxifene; D007371:Interferon-gamma; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases