Objective To investigate the effect of interleukin-1β(IL-1β)on expression and activity of matrix metallopmteinage-2(MMP-2)of cultured human cardiac fibroblasts and related signaling pathway.Methods Primary human cardiac fibmblasts seeded in 6-well tissue culture plates and cultured to 80%to 90%confluence were harvested at passage 3 to 6 and exposed to IL-1β at vaious concentrations for 24 h,culture supernatant and cell protein were obtained.MMP-2 mRNA was determined by RT-PCR.The activity of MMP-2 wag analyzed by zymography and the expression of inducible nitric oxide synthese(iNOS)Drotein level was detected by Western blot analysis.Assessment of NO production in the culture supernatant wag performed using the Griess method.Results IL-1β(4 ng/ml)significandy increased MMP-2 activity of cultured fibmblagts in a time-dependent manner.MMP-2 mRNA expression wag significantly upregulated by IL-1β(4 ng/ml and 10 ng/ml,all P＜0.01).Moreover,IL-1β also significantly increased NO production in supernatant(P＜0.01)and these effects could be significantly blocked by cotreatment with L-NMMA(10-3 mol/L,all P＜0.01).Western blot analysis showed that iNOS could not be detected in unstimulated human cardiac fibroblasts but could be detected in cardiac fibroblasts exposed to IL-1β.Conclusion IL-1β increased MMP-2 activity and transcription of human cardiac fibroblasts via iNOS-NO