Overactivation of IL-4-induced activator protein-1 in atopic dermatitis.
Atopic dermatitis is regarded as mediated by Th2-type immunity. In fact, it frequently coincides with the elevation of immunoglobulin (Ig)-E in patients' sera. Due to the pivotal role of interleukin (IL)-4 in regulation of IgE, we hypothesized if atopic dermatitis represents a hyper-reactive condition in response to IL-4 when it coincides the higher serum level of IgE. To address this possibility, peripheral blood mononuclear cells (PBMC) isolated from patients with atopic dermatitis with the high serum IgE level, from those with psoriasis or from healthy volunteers were stimulated with recombinant IL-4 and analyzed for activation of transcription factors including activator protein (AP)-1 or signal transducers and activators of transcription (STAT)-6 by employing electrophoretic mobility shift assays. Although no significant difference between atopy patients and other groups was observed in the STAT-6 binding activity in IL-4-stimulated PBMC, it over-activated the binding of AP-1 in PBMC of the patients with atopic dermatitis. The AP-1 binding was interfered by the use of an antibody directed against JunB. This is the indication that IL-4-overactivated AP-1 is composed of JunB. Furthermore, semi-quantitative RT-PCR analyses revealed marked down-modulation of a Th1 cytokine, interferon (IFN)-gamma, in IL-4-stimulated PBMC derived from atopy patients, but not that from healthy individuals. Together, our present study indicates that AP-1 is over-activated by IL-4 in PBMC of the atopic patients with the higher IgE level, thereby implying that IL-4-induced over-activation of AP-1 might be one of pathogenic factors in atopic dermatitis.
Yamazaki
Fumie
F
Department of Dermatology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama-shi, 589-8511 Osaka, Japan.
Aragane
Yoshinori
Y
Maeda
Akira
A
Matsushita
Kiyomi
K
Ueno
Kengo
K
Yudate
Tatsuo
T
Kawada
Akira
A
Tezuka
Tadashi
T
D003876:Dermatitis, Atopic / Q000097:blood*; D015536:Down-Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism; D011565:Psoriasis / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000097:blood*
D012333:RNA, Messenger; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D015847:Interleukin-4; D007371:Interferon-gamma