Lipopolysaccharides activates MMP-2 in MCF-7-MMP-2 via MT-MMP independent pathway

Our previous study showed that LPS of A. actinomycetemcomitans activated MMP-2 in human periodontal ligament (HPDL) cells and the activation was serine protease-dependent pathway (J Periodontal 2004;75:1647-54). Objective: To determine whether the activation of MMP-2 by LPS requires MT-MMP. Methods: Bacterial LPS was added into the culture of MCF-7-MMP-2, the breast cancer cell line that does not express MT-MMP, for 48 hours in serum-free condition. The cytotoxicity of the LPS was assayed by methylene blue staining and the level of MMP-2 activation was measured by gelatin zymography. Results: Bacterial LPS at the non-toxic level could activate MMP-2 in MCF-7-MMP-2 cell line. Furthermore, the activation could be inhibited by aprotinin, a serine protease inhibitor, and PTDC, an NF-kB inhibitor. Conclusion: The activation of MMP-2 by LPS can occur without the presence of MT-MMP and appears to mediate through a serine protease dependent pathway. This work was supported by Dental Research Fund, Dental Research Project 3205-312 #1/2004, Faculty of Dentistry, Chulalongkorn University.