Clinical significance of MIF/AP-1/MMP-9 signaling pathway expression in peripheral blood of children with Kawasaki disease / 国际儿科学杂志

ABSTRACT

Objective:To study the relationship of macrophage migration inhibitory factor(MIF)/activator protein-1(AP-1)/matrix metalloproteinase-9(MMP-9)expression with inflammatory response and coronary artery lesion(CAL)in Kawasaki disease(KD).Methods:Forty-six children with KD were enrolled as the KD group, and divided into CAL group( n=17)and non-coronary artery lesion(NCAL)group( n=29). Fifteen age-and gender-matched children with lower respiratory infections and twenty children for selective operation were chosen as the control groups.Fluorescence quantitative PCR and Western blot were used to detect c-Jun/c-Fos mRNA and protein expression respectively.Serum levels of MIF/phospho-c-Jun/MMP-9 were measured by ELISA. Results:The c-Jun/c-Fos mRNA and protein expression as well as phospho-c-Jun level increased significantly in acute phase of KD as compared with those in control groups(comparison between groups c-Jun mRNA F=654.318, P<0.001; c-Fos mRNA F=580.998, P<0.001; phospho-c-Jun F=74.756, P<0.001; all P<0.05), and they were even higher in the CAL group(c-Jun mRNA t=6.820, P<0.001; c-Fos mRNA t=8.047, P<0.001; phospho-c-Jun t=2.361, P=0.029; all P<0.05), then decreased in subacute phase.Serum protein levels of MIF and MMP-9 in acute phase of KD were higher than those of control groups(comparison between groups MIF F=104.008, P<0.001; MMP-9 F=182.798, P<0.001), and much higher in CAL group than those in NCAL group(MIF t=2.163, P=0.043; MMP-9 t=2.104, P=0.048). There were positive correlations among serum MIF, phospho-c-Jun and MMP-9 in acute phase of KD(MIF and phospho-c-Jun r=0.552, P<0.001; phospho-c-Jun and MMP-9 r=0.731, P<0.001; MIF and MMP-9 r=0.421, P=0.004). Conclusion:MIF/AP-1/MMP-9 signaling pathway may participate in the pathological progress of KD vasculitis and CAL.AP-1 expression and activation level in acute phase may be helpful to assess the inflammatory status and to predict CAL.