39P - IL-6 induces and releasing of MMP-9 in murine bone marrow neutrophils by activating STAT3 pathway

Abstract

To investigate the production and release of murine bone marrow neutrophil MMP-9 and its mechanism of activation. Murine bone marrow neutrophils were separated and cultured in vitro and randomly divided into four groups: control group, IL-6 50ng/ml stimulation group, IL-6 50ng/ml + DMSO group and IL-6 50ng/ml + STAT3 inhibitor VIII 50 µM group. RT-PCR method was used to evaluate the mRNA level of intracellular MMP-9 of neutrophils. Gelatin zymography was performed to detect the activity of MMP-9 released from neutrophils. Western blot was applied to test the phosphorylation levels of STAT3 pathway in neutrophils. Compared with the control group, the administration of IL-6 enhanced the mRNA expression of MMP-9 (P = 0.0050); the activity of MMP-9 released from neutrophils was elevated (P = 0.0087) and the p-STAT3 levels in neutrophils was also increased (P =0.089). After the STAT3 inhibitor VIII was added, the mRNA expression of MMP-9, the activities of MMP-9 in the supernatant and the p-STAT3 levels in neutrophils were decreased significantly compared with those in the IL-6 group (P = 0.0067, 0.048 and 0.098, respectively). IL-6 induces the production and releasing of MMP-9 in neutrophils and the effect may be induced by the activation of STAT3 pathway.