Induction of synthesis of matrix metalloproteinases by interleukin-6; evidence for hepatic regeneration following hemi-hepatectomy

AIM OF THE STUDY: Interleukin-6 (IL-6) can play a role in hepatic regeneration through many mechanisms, one of which is the induction of synthesis of matrix metalloproteinases (MMPs). The aim of the study is to focus on the significance and role of MMPs in the regenerative process to reveal the correlation between IL-6 and MMPs in rats following partial hepatectomy. MATERIAL AND METHODS: Following hemi-hepatectomy, eighty male rats were divided into a control group and a group treated with IL-6 35 µg/100 gm body weight according to a lethality study. The blood samples were drawn from all animal groups for MMP-9 serum level assessment. For the quantitative determination of MMP-9 an enzyme-linked immunosorbent assay (ELISA) was used (Cytoimmune Science Inc., MD) through the quantitative sandwich immunosorbent assay technique. A monoclonal antibody for MMP-9 was pre-coated onto microplate standards. After washing away the unbound substances, an enzyme-linked polyclonal antibody specific for cytokine was added to the wells and color developed in proportion to the amount of total cytokine (pro and/or active) bound in the initial step. The color development was stopped and the intensity of the color was measured. RESULTS: The liver regeneration rate (%) was significantly higher in the group of rats treated with IL-6 (median value was 49.55% vs. 33.20%), p < 0.001. The MMPs’ serum level was significantly higher in the group of rats with resection and treatment (median value was 8.01). CONCLUSIONS: These results give evidence for the vital role of MMPs in the process of hepatic regeneration, the level of which, in turn, has a close relationship with the level of IL-6. MMPs have diverse effects in promoting angiogenesis, remodeling of extracellular matrix and endothelial cell proliferation.