Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 285, Issue 3, Pages 170-178Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2015.04.007
Keywords
Platelet Derived Growth Factor-beta (PDGF-B); Aryl hydrocarbon receptor; Diesel exhaust particles; Macrophage polarization; Lung fibroblasts
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Funding
- Fondation Coeur et Arteres [FCA 09T3]
- Institut National de la Sante et de la Recherche Medicale
- University of Rennes 1
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Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (M Phi) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing M Phi. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantly increased mRNA expression of PDGF-B in M1 M Phi, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from M Phi culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-R beta, Ala and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MC Phi, strongly suggesting that the PDGF-BB secreted by DEPe-exposed M Phi is sufficient to activate the PDGF-R beta pathway of human lung fibroblasts. In conclusion, we demonstrated that human M Phi, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. (C) 2015 Elsevier Inc. All rights reserved.
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