Monocyte Chemoattractant Protein-1 Deficiency Attenuates Oxidative Stress and Protects against Ovariectomy-Induced Chronic Inflammation in Mice |
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| Authors: | Woon-Ki Kim Eun-Kyung Choi Ok-Joo Sul Yeon-Kyung Park Eun-Sook Kim Rina Yu Jae-Hee Suh Hye-Seon Choi |
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| Institution: | 1. Department of Biological Sciences, University of Ulsan, Ulsan, Korea.; 2. Department of Endocrinology, Ulsan University Hospital, Ulsan, Korea.; 3. Department of Food Science and Nutrition, University of Ulsan, Ulsan, Korea.; 4. Department of Pathology, Ulsan University Hospital, Ulsan, Korea.; The Chinese University of Hong Kong, Hong Kong, |
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| Abstract: | BackgroundLoss of ovarian function is highly associated with an elevated risk of metabolic disease. Monocyte chemoattractant protein-1 (MCP-1, C-C chemokine ligand 2) plays critical roles in the development of inflammation, but its role in ovariectomy (OVX)-induced metabolic disturbance has not been known.Methodology and Principal FindingsWe investigated the role of MCP-1 in OVX-induced metabolic perturbation using MCP-1-knockout mice. OVX increased fat mass, serum levels of MCP-1, macrophage-colony stimulating factor (M-CSF), and reactive oxygen species (ROS), whereas MCP-1 deficiency attenuated these. OVX-induced increases of visceral fat resulted in elevated levels of highly inflammatory CD11c-expressing cells as well as other immune cells in adipose tissue, whereas a lack of MCP-1 significantly reduced all of these levels. MCP-1 deficiency attenuated activation of phospholipase Cγ2, transforming oncogene from Ak strain, and extracellular signal-regulated kinase as well as generation of ROS, which is required for up-regulating CD11c expression upon M-CSF stimulation in bone marrow-derived macrophages.Conclusions/SignificanceOur data suggested that MCP-1 plays a key role in developing metabolic perturbation caused by a loss of ovarian functions through elevating CD11c expression via ROS generation. |
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