Inflammation, endoplasmic reticulum stress, autophagy, and the monocyte chemoattractant protein-1/CCR2 pathway.
Numerous inflammatory cytokines have been implicated in the pathogenesis of cardiovascular diseases. Monocyte chemoattractant protein (MCP)-1/CCL2 is expressed by mainly inflammatory cells and stromal cells such as endothelial cells, and its expression is upregulated after proinflammatory stimuli and tissue injury. MCP-1 can function as a traditional chemotactic cytokine and also regulates gene transcription. The recently discovered novel zinc-finger protein, called MCPIP (MCP-1-induced protein), initiates a series of signaling events that causes oxidative and endoplasmic reticulum (ER) stress, leading to autophagy that can result in cell death or differentiation, depending on the cellular context. After a brief review of the basic processes involved in inflammation, ER stress, and autophagy, the recently elucidated role of MCP-1 and MCPIP in inflammatory diseases is reviewed. MCPIP was found to be able to control inflammatory response by inhibition of nuclear factor-κB activation through its deubiquitinase activity or by degradation of mRNA encoding a set of inflammatory cytokines through its RNase activity. The potential inclusion of such a novel deubiquitinase in the emerging anti-inflammatory strategies for the treatment of inflammation-related diseases such as cardiovascular diseases and type 2 diabetes is briefly discussed.
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA. pk@ucf.edu
Pappachan E
PE
Kolattukudy
Jianli
J
Niu
D001343:Autophagy / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D054390:Receptors, CCR2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology
D018932:Chemokine CCL2; D054390:Receptors, CCR2