A Role Of Nfat Subtypes: NFAT1and NFAT2in Regulating Th2Cytokines

Background: Nuclear factor of activated T cells （NFAT）, including NFAT1to NFAT5five members, plays a pivotal role in T lymphocytes activation. Among the fivesubtypes, NFAT1, NFAT2were recognized as the key transcript factors of allergicdiseases. However, the results of studies on the functions of NFAT1and NFAT2inTh2cells are still conflicting. Therefore, we made this study to investigate thefunctions of NFAT1and NFAT2in Th2lymphocytes.Methods: NFAT1and NFAT2of mouse Th2lymphocyte cell line （D10.G4.1） wereknocked out respectively using NFAT1and NFAT2small interfering RNA （siRNA）.Real-time PCR was employed to evaluate the mRNA levels of NFAT1, NFAT2,GATA3and Th2cytokines, such as IL-4, IL-5, IL-13.Results: NFAT1, NFAT2, GATA3, IL-4, IL-5, IL13mRNA were detectable in D10cells. SiRNA could respectively suppress the gene expression of NFAT1and NFAT2in mRNA levels in D10cells. Higher levels of IL-4, IL-5and IL-13were expressed inNFAT1siRNA treated Th2cells, which suggested NFAT1might play a negative rolein Th2cytokines expression. However, an invert phenomenon was shown in NFAT2siRNA treated Th2cells, that NFAT2siRNA could down-regulate IL-4mRNA andIL-13mRNA levels, in addition, IL-4mRNA decreased significantly （P<0.01）, aswell as the GATA3mRNA level.Conclusions: NFAT1may play a negative role in regulating Th2cytokines geneexpression and NFAT2may have the opposite effect. Background: The measurement of hydrogen peroxide （H₂O₂） in exhaled breathcondensate（EBC）has been proposed as a noninvasive way of monitoring airwayinflammation. However, results from individual studies on EBC H₂O₂evaluation ofasthma are conflicting. The purpose of this meta-analysis was to explore whetherEBC H₂O₂is elevated in asthmatics, and whether it reflects disease severity, controlor response to corticosteroid treatment.Methods: Studies were identified by searching PubMed, Embase, CochraneDatabase, CINAHL and www.controlled-trials.com for relevant reports published beforeJuly2010. Observational studies comparing levels of EBC H₂O₂betweennon-smoking asthmatics and healthy subjects were included. Data were independentlyextracted by two investigators and analyzed by Stata10.Results: Eight studies （involving728participants） were included. EBC H₂O₂concetnrations were significantly higher in nonsmoking asthmatic patients comparedto healthy subjects and higher values of EBC H₂O₂were observed at each level ofasthma classified either by severity or control level and the values were negativelycorrelated with FEV1. In addition, EBC H₂O₂concetnrations were lower incorticosteroid-treated asthmatics than in patients not treated with corticosteroids.Conclusions: H₂O₂might be a promising biomarker for guiding asthmamanagement, however, further investigation is needed to establish its role.