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AIM: To study the relationship between interleukin-1beta (IL-1β) up-regulating tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1) mRNA expression and phosphorylation of both c-jun N-terminal kinase (JNK) and p38 in rat hepatic stellate cells (HSC).METHODS: RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC.RESULTS: TIMMP-1 mRNA expression (1.191± 0.079)was much higher after treatment with IL-1β (10 ng/mL)for 24 h than in control group (0.545 ± 0.091) (P＜0.01).IL-1β activated JNK and p38 in a time-dependent manner.After stimulation with IL-1β for 0, 5, 15, 30, 60 and 120min, the JNK activity was 0.982 ±0.299, 1.501 ± 0.720,2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385±0.368, respectively. There was a significant difference in JNK activity at 15 min (P＜ 0.01), 30 min (P＜ 0.01)and 60 min (P＜0.01) in comparison to that at 0 min.The p38 activity was 1.061±0.310, 2.050±0.863,2.380±0.573, 2.973±0.953, 2.421±0.793, and1.755 ± 0.433 at the 6 time points (0, 5, 15, 30, 60 and 120 min) respectively. There was a significant difference in p38 activity at 5 min (P＜0.05), 15 min (P＜0.01), 30min (P＜0.01) and 60 min (P＜0.01) compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 (10 μmol/L, 1.022 ± 0.113; 20 μmol/L,0.869±0.070; 40 μmol/L, 0.666±0.123). Their decreases were all significant (P＜0.05, P＜0.01, P＜0.01)in comparison to control group (without SP600125 treatment, 1.163±0.107). In the other 3 groups pretreated with different concentrations of SB203580 (10 μmol/L,1.507±0.099; 20 μmol/L, 1.698±0.107; 40 μmol/L,1.857 ±0.054), the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group (without SB203580 treatment, 1.027 ± 0.061)with a significant statistical significance (P＜ 0.01).CONCLUSION: IL-1β has a direct action on hepatic fibrosis by up-regulating TIMMP-1 mRNA expression in rat HSC.JNK and p38 mitogen-activated protein kinases (MAPKs) are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and JNK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC.