Up-regulation of interleukin-13 receptor alpha1 on human keratinocytes in the skin of psoriasis and atopic dermatitis.
BACKGROUND
Interleukin (IL)-13 is a pleiotropic cytokine, which shares many biological functions with IL-4. The receptor subunits of IL-13 consist of IL-4Ralpha, IL-13Ralpha1 and IL-13Ralpha2. The regulatory mechanisms of the IL-13Ralpha expression in the keratinocytes of certain skin disease have not been known.


OBJECTIVE
To clear the roles of IL-13 and the regulatory mechanisms of its receptor in atopic dermatitis (AD) and psoriasis.


METHODS
The expression of IL-13Ralpha1 in the skin of AD and psoriasis was investigated by immunohistochemistry. The regulation of IL-13Ralpha mRNA in the skin and human primary keratinocyte (HPK) was investigated by quantitative PCR. The secretion of IL-6 and RANTES from HPK was measured by ELISA.


RESULTS
The expression of IL-13Ralpha1 was more prominent on the suprabasal keratinocytes in the skin of AD and striking increase of staining was observed on all layers of keratinocyte in the skin of psoriasis. The mRNA of IL-13Ralpha1, but not of IL-13Ralpha2 was overexpressed in both skin of AD and psoriasis. In vitro experiment using HPK demonstrated that IFN-gamma, IL-13 but not IL-4 could up-regulate the mRNA expression of IL-13Ralpha1. In contrast, IL-13Ralpha2 mRNA expression was up-regulated by IFN-gamma plus IL-4. Furthermore, the stimulation of HPK with IFN-gamma plus IL-13 and/or IL-4 resulted in significant enhancement of IL-6 and RANTES secretion.


CONCLUSIONS
These findings indicate that IL-4 and IL-13 have different regulatory effects on the expression of IL-13Ralpha1 and alpha2, and the overexpression of IL-13Ralpha1 may play some roles in the pathogenesis of chronic stage of AD or psoriasis.
Wongpiyabovorn
Jongkonnee
J
Department of Dermatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Suto
Hajime
H
Ushio
Hiroko
H
Izuhara
Kenji
K
Mitsuishi
Koichi
K
Ikeda
Shigaku
S
Nakao
Atsuhito
A
Okumura
Ko
K
Ogawa
Hideoki
H
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D012867:Skin / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; C508181:IL13RA1 protein, human; D018836:Inflammation Mediators; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D020033:Protein Isoforms; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D015847:Interleukin-4; D007371:Interferon-gamma