Differential expression of mRNA for Th1 and Th2 cytokine-associated transcription factors and suppressors of cytokine signalling in peripheral blood mononuclear cells of patients with atopic dermatitis.
Atopic dermatitis is characterized by Th2-dominant immunity. Recently many intracellular molecules have been reported to regulate cytokine expression and T cell differentiation. GATA-3 and T-box expressed in T cells (T-bet) are transcription factors that play a critical role in the development of Th2 and Th1 immunity, respectively. Suppressor of cytokine signalling (SOCS)-3 and SOCS-5, are negative regulators of the cytokine signalling induced by IL-12 and IL-4, respectively. Txk is a transcription factor that activates IFN-gamma gene directly. The present study was designed to identify intracellular molecules that are responsible for the pathogenesis and the imbalance of cytokines in atopic dermatitis. Semi-quantitative RT-PCR revealed that in peripheral blood mononuclear cells without any stimulation the levels of mRNA for GATA-3 and SOCS-3 were elevated, the levels of mRNA for Txk were depressed and the levels of mRNA for T-bet and SOCS-5 were comparable in patients with atopic dermatitis as compared with healthy controls. In addition, successful therapy normalized levels of mRNA for GATA-3 and Txk, although those for the others including IL-4, IL-5, IL-10, IL-13 and IFN-gamma did not change. Levels of Txk mRNA correlated with those of IFN-gamma, while the mRNA levels of the other regulators did not correlate with those of any of the cytokines. These results suggest GATA-3 and Txk might be involved in skin lesions, while SOCS-3 might be associated with an imbalance of cytokines that is difficult to normalize in atopic dermatitis.
Arakawa
S
S
Department of Anatomy, Biology and Medicine (Dermatology), Faculty of Medicine, Oita University, Oita, Japan. arakawa@med.oita-u.ac.jp
Hatano
Y
Y
Katagiri
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology; D005260:Female; D050990:GATA3 Transcription Factor; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D012871:Skin Diseases / Q000235:genetics / Q000276:immunology; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016335:Zinc Fingers; D000098815:T-bet Transcription Factor
D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors