title: Effects of monocyte-endothelium interactions on the expression of type IV collagenases in monocytes.
abstract: The adhesion of monocytes to endothelial cells is one of the early stages in the development of atherosclerosis. The expression of type IV collagenases, which include matrix metalloproteinase (MMP)-2 and MMP-9, in monocytes is hypothesized to play an important role in monocyte infiltration and transformation into foam cells. The aim of the present study was to examine the effects of monocyte-endothelium interactions on the expression levels of type IV collagenases and their specific inhibitors in monocytes, and to investigate the roles of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in this process. Monocytes were single-cultured or co-cultured with endothelial cells. The expression of the type IV collagenases, MMP-2 and MMP-9, and their specific inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, in monocytes was determined by immunohistochemistry followed by image analysis. The expression levels of MMP-2 and MMP-9 were found to be low in the single-culture monocytes, but increased significantly when the monocytes and endothelial cells were co-cultured. However, treatment with monoclonal TNF-α or IL-1β antibodies partially inhibited the upregulated expression of MMP-2 and MMP-9 in the co-cultured monocytes. Expression of TIMP-1 and TIMP-2 was observed in the single monocyte culture, and a small increase in the expression levels was observed when the monocytes were co-cultured with endothelial cells. Therefore, monocyte-endothlium interactions were shown to increase the expression of type IV collagenases in monocytes, resulting in the loss of balance between MMP-2 and -9 with TIMP-1 and -2. In addition, TNF-α and IL-1β were demonstrated to play important roles in this process.
authors.affiliation: Department of Cardiology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Yong-Qin
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Xue
authors.affiliation: Department of Cardiology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Gao
authors.affiliation: Department of Cardiology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xiao-San
authors.initials: XS
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Cong-Xia
authors.initials: CX
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yu-Bai
authors.initials: YB
authors.lastname: Yang
keywords: atherosclerosis; collagenase IV; endothelium; interleukin-1β; monocyte; tumor necrosis factor-α