Relationship Between Overactive IL-4/IL-4R Pathway And T Cell-Specific Transcription Factors STAT4/STAT6 In Asthma

Objective To identify the existence of overactive IL-4/IL-4R pathway in asthma, explore the relationship between the pathway and transcription factors STAT4/STAT6, and clarify the complicated immune pathogenesis of asthma further.Methods The expressions of STAT4 and STAT6 mRNA in lymphocytes were assayed by RT-PCR. pSTAT4 and pSTAT6 expressions were assayed by IF in 25 asthmatic patients pre- and post- intervention by mhIL-4RAb and 30 healthy children. IL-4 and IFN-γconcentrations in the supernatant of PBMC were detected by ELISA.Results IL-4 concentration in the lymphocyte supernatant of asthmatic group was (497.21±229.37)pg/ml, which was significantly elevated compared to that of intervention group (218.63±121.19) pg/ml (q=-6.6506,P<.0001) and control group (142.07±56.45) pg/ml (q=8.92103,P<.0001). No significant difference was demonstrated between intervention group and control group (q=-1.9232, P=0.0581). Significantly lower concentration of IFN-γin asthmatic group was detected as compared to intervention group and control group [(5094.44±2437.67)pg/ml vs. (6670.14±3167.27) pg/ml(q=2.1554,P=0.0341) and (6993.36±2283.49) pg/ml (q=2.7091,P=0.0082)], but no difference was found between intervention group and control group (q=0.4611,P=0.6460). RT-PCR results revealed that STAT4 mRNA expression were 0.70±0.17 in asthmatic group,0.85±0.24 in intervention group and 0.92±0.29 in control group; while asthmatic group was significantly distinct to intervention group (q=2.1991,P=0.0308) and control group(q=3.2905,P=0.0015) and no difference between intervention group and control group (q=0.9970,P=0.3218) .The levels of STAT6 mRNA expression were 1.09±0.20 in asthmatic group,0.94±0.16 in intervention group and 0.85±0.22 in control group; Asthmatic group was significantly distinct to intervention group (q=-2.7281, P=0.0078) and control group (q=-4.6270, P<.0001) and no difference between intervention group and control group (q=-1.7818, P=0.0786). According to the results of IF, pSTAT4 expression were 181824.67±26782.80 in asthmatic group,483523.20±56546.58 in intervention group and 519225.13±60085.59 in control group. The expression of pSTAT4 in asthmatic group was significantly declined compared to intervention group (q=16.50, P<.0001) and control group (q=18.45, P<.0001). No differences were found between intervention group and control group (q=1.95, P=0.0576). pSTAT6 expression was 82559.40±4166.63 in asthmatic group,45583.20±3672.16 in intervention group and 42284.13±6588.10 in control group. The expression of pSTAT6 in asthmatic group was significantly increased compared to intervention group (q=-20.35, P<.0001) and control group (q=-22.171, P=<.0001). No difference was found between intervention group and control group (q=-1.82, P=0.0765).Conclusions In asthmatic subjects there is a tendency of Th2 polarization with over-production of Th2-like cytokines, which is regulated by two reversely worked active transcription factors: pSTAT4 and pSTAT6. mhIL-4RAb can influence expression of pSTAT4 and pSTAT6 through blocking IL-4/IL-4R pathway to restore the balance of Th1/ Th2. IL-4 and IFN-γin signal pathway of IL-4/IL-4R can reversely influence transcription of STAT6 and STAT4.