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Matrix metalloproteinase-2 and -9 are induced differently by metal nanoparticles in.pdf

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Matrix metalloproteinase-2 and -9 are induced differently by metal nanoparticles in

Matrix metalloproteinase-2 and -9 are induced differently by metal nanoparticles in human monocytes: The role of oxidative stress and protein tyrosine kinase activation Rong Wan a,d,1, Yiqun Mo a,1, Xing Zhang b, Sufan Chien c, David J. Tollerud a, Qunwei Zhang a,? a Department of Environmental Health and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 555 South Floyd Street, Louisville, KY 40202, USA b Department of Hygiene, Zhejiang Academy of Medical Sciences, Zhejiang, PR China c Department of Surgery, University of Louisville, Louisville, KY, USA d Department of Pathology, Fujian Medical University, Fujian, PR China a b s t r a c ta r t i c l e i n f o Article history: Received 17 June 2008 Revised 22 August 2008 Accepted 26 August 2008 Available online 16 September 2008 Keywords: Metal nanoparticles Matrix metalloproteinases Human monocyte cell line U937 Tissue inhibitors of metalloproteinases Recently, many studies have shown that nanoparticles can translocate from the lungs to the circulatory system. As a particulate foreign body, nanoparticles could induce host responses such as reactive oxygen species (ROS) generation, inflammatory cytokine and matrix metalloproteinase (MMP) release which play a major role in tissue destruction and remodeling. However, the direct effects of nanoparticles on leukocytes, especially monocytes, are still unclear. The objective of the present study was to compare the ability of Nano- Co and Nano-TiO2 to cause alteration of transcription and activity of MMPs and to explore possible mechanisms. We hypothesized that non-toxic doses of some transition metal nanoparticles stimulate an imbalance of MMP/TIMP that cause MMP production that may contribute to their health effects. To test this hypothesis, U937 cells were treated with Nano-Co and Nano-TiO2 and cytotoxic effects and ROS generation were measured. The alteration of MMP-2 and MMP-9 expression and activity of MMP-2 and