Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: roles of PPARγ and Th2 cytokines

Yakeu, G., Butcher, L., Isa, S., Webb, R., Roberts, Aled Wyn, Thomas, A.W., Backx, Karianne, James, Philip Eurig and Morris, K. 2010. Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: roles of PPARγ and Th2 cytokines. Atherosclerosis 212 (2) , pp. 668-673. 10.1016/j.atherosclerosis.2010.07.002

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Abstract

Objective Pharmacological activation of the nuclear receptor PPARγ is linked to numerous beneficial effects in the contexts of inflammation, lipid homeostasis, Type-2 Diabetes (T2D) and atherosclerosis. These beneficial effects include priming of circulating monocytes for differentiation towards an ‘alternative’ anti-inflammatory M2 macrophage phenotype. As we have recently shown that participation in low-intensity exercise increases PPARγ expression and activity in leukocytes from previously sedentary individuals, we aimed to elucidate whether low-intensity exercise elicited a pattern of gene expression similar to that reported for M2 monocyte-macrophage differentiation. Methods 17 sedentary individuals undertook an 8-week low-intensity exercise programme (walking 10,000 steps/day, three times/week). Changes in expression of PPARs and the PPARγ co-activators PGC-1α and PGC-1β; Th2 (IL-4; IL-10) and Th1 (IL-6) cytokines; and markers for the M2 (AMAC1, CD14, MR, IL-4) and the ‘classical’ pro-inflammatory M1 (MCP-1, TNFα, IL-6) phenotypes, were determined using RT-PCR (to assess leukocyte mRNA expression) and ELISA (to assess plasma cytokine levels). Results Exercise was associated with upregulation of M2 markers, PGC-1α and PGC-1β, and with downregulation of M1 markers. Moreover, plasma levels of Th2 cytokines increased after exercise, while those of Th1 cytokines decreased. However, other PPARs (PPARα; PPARβ/δ) did not undergo marked exercise-induced activation or upregulation. Thus, participation in low-intensity exercise may prime monocytes for differentiation towards an M2 macrophage phenotype via PPARγ/PGC-1α/β. Conclusion Given the similarities between these effects and pharmacologically induced M2 polarisation, we propose that exercise-induced PPARγ/PGC-1α/β-mediated M2 polarisation may constitute a novel anti-inflammatory benefit of low-intensity exercise.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	exercise, monocyte polarisation, anti-inflammatory, anti-atherogenic, PPARγ
Publisher:	Elsevier
ISSN:	0021-9150
Last Modified:	05 Jun 2022 07:28
URI:	https://orca.cardiff.ac.uk/id/eprint/23808

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