Background Intedeukin-13 (IL-13) is recognized to be a key modulator in the pathogenesis of Th2-induced allergic inflammation. Transcription factors GATA3 and NFAT1 have been both implicated in the regulation of Th2 cytokines. We previously demonstrated the GATA3-NFAT1 association during human T cell activation. However, the function of the GATA3-NFAT1 complex in Th2 cytokines regulation is still unknown. Small interference RNA (siRNA) was constructed to knock down GATA3 expression in Hut-78 cells to investigate the possible role of GATA3-NFAT1 complex in IL-13 transcription.Methods Cells were stimulated with anti-CD3 plus anti-CD28 antibodies to mimic in vivo antigen-mediated co-stimulation; the expression of IL-13 mRNA was determined by real-time PCR; chromation immunoprecipitation (CHIP) assay was employed to investigate the NFAT1 binding to IL-13 promoter. Results GATA3 siRNA suppressed the expression of GATA3 both in mRNA and protein levels in Hut-78 cells. The binding of NFAT1 to IL-13 promoter was inhibited by GATA3 siRNA in activated T cells, which was followed by the reduction of IL-13 transcription.Conclusion GATA3-NFAT1 complex may play an important role in the regulation of IL-13 transcription in human T cells.
YAO Xin YANG Yan HE Hai-yan WANG Min YIN Kai-sheng HUANG Mao
Aarsenic trioxide (AT) has a long history of use in both traditional Chinese medicine and in modem medicine in asthma therapy. Recently, Yin et al' found that AT even at small doses reduced the airway inflammation of sensitized guinea pigs. However the mechanism underlying this is still largely unknown. Interleukin 13 (IL-13), as one of the important TH2 cytokines, plays an important role in asthma pathogenesis through promoting eosinophilic inflammation,
YAO Xin HE Hai-yan YANG Yan DAI Shan-lin SUN Pei-li YIN Kai-sheng HUANG Mao