Monocyte Chemoattractant Protein-1 Deficiency Attenuates Oxidative Stress and Protects against Ovariectomy-Induced Chronic Inflammation in Mice.

Kim, Woon-Ki; Choi, Eun-Kyung; Sul, Ok-Joo; Park, Yeon-Kyung; Kim, Eun-Sook; Yu, Rina; Suh, Jae-Hee; Choi, Hye-Seon

Background: Loss 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 Findings: We 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/Significance: Our 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.

MONOCYTE chemotactic factor; PROTEIN deficiency; OXIDATIVE stress; METABOLIC disorders; OVARIECTOMY; INFLAMMATION; LABORATORY mice; GRANULOCYTE-macrophage colony-stimulating factor; DISEASE risk factors

PLoS ONE, 2013, Vol 8, Issue 8, p1

1932-6203

Academic Journal

10.1371/journal.pone.0072108