The effect of ppar-gamma ligands on monocyte polarisation.
Cardiff Metropolitan University
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Pharmacological activation of the nuclear receptor PPARγ enhances differentiation of circulating monocytes towards an alternative anti-inflammatory M2 phenotype, linked to atherosclerosis and its cardiovascular complications. Previous work done by Butcher et al., (2008) has shown that participation in low-intensity exercise exerts a significant increase in PPARγ expression and activity in the leukocytes of previously sedentary individuals. Seventeen inactive adults within a mean age range of 45.6 ± 11.1 years took part in low intensity exercise programme for a period of eight weeks by walking 10000 steps thrice weekly. There was a significant down-regulation in leukocytes mRNA gene expression of the pro-inflammatory M1 markers (MCP-1 and IL-6), and an up-regulation in gene expression of the M2 markers of monocyte polarisation: MR, CD163 and CX3CR1 after 8 weeks of exercise when compared to controls. There was also a significant increase in mRNA gene expression of the Th2 cytokine IL-4 as a result of this exercise regimen. In-vitro differentiation of monocytes into the M2 phenotype by PPARγ activation was achieved by treating THP-I monocytic cells for up to 72 hours with the Th2 cytokine IL-13 (15ng/ml), the dietary lipid CLA (20 or 100µM) and a specific PPARy ligand Rosiglitazone (1µM). Monocytes were polarised to an M2 phenotype after IL-13 treatment, inducing an increase in mRNA gene expression of MR and a decrease in MCP-I gene expression; these effects were further enhanced after 72 hours of incubation upon co-treatment of IL-13 with CLA or Rosiglitazone. Also, polarisation of differentiated THP-1 cells to an M2 phenotype and treatment with the various stimuli resulted in a significant increase in MR and CD163 surface expression. Interestingly the down-regulation of MCP-1 with Rosiglitazone and CLA was abolished by treatment with the PPARy antagonist GW9662 (1µM). In conclusion, this study presents evidence that exercise and the dietary lipid CLA can induce monocyte polarisation towards a beneficial M2 phenotype partly through their ability to activate PPARy.
MSc Biomedical Science
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An investigation into the role of PPARγ and IL-6 in exercise-induced alterations in monocyte gene expression Ruffino, José (Cardiff Metropolitan University, 2015)The pro-inflammatory M1 macrophage phenotype is linked to insulin resistance, T2D and associated cardiovascular co-morbidities, whereas M2 macrophages regulate the M1 inflammatory response and are, thus, believed to be ...
Yakeu, Gertrude (University of WalesCardiff School of Health Sciences, 2010)Pharmacological activation of the nuclear receptor PPARγ enhances differentiation of circulating monocytes towards an alternative anti-inflammatory M2 phenotype, linked to atherosclerosis and its cardiovascular complications. ...
Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: Roles of PPARy and Th2 cytokines Yakeu, G.; Butcher, Lee; Isa, S.A.; Webb, Richard; Roberts, Aled W.; Thomas, Andrew; Backx, Karianne; James, Philip; Morris, Keith (Elsevier, 2010)Objective: Pharmacological activation of the nuclear receptor PPAR is linked to numerous beneficial effects in the contexts of inflammation, lipid homeostasis, Type-2 Diabetes (T2D) and atherosclerosis. These beneficial ...