Exposure to Diesel Exhaust Particle Extracts (DEPe) Impairs Some Polarization Markers and Functions of Human Macrophages through Activation of AhR and Nrf2: e0116560

• Published in: PloS one Vol. 10; no. 2
• Main Authors: Jaguin, Marie, Fardel, Olivier, Lecureur, Valerie
• Format: Journal Article
• Language: English
• Published: 01-02-2015
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0116560

Macrophages (M Phi ), well-known to play an important role in immune response, also respond to environmental toxic chemicals such as diesel exhaust particles (DEP). Potential effects of DEPs towards M Phi polarization, a key hall-mark of M Phi physiology, remain however poorly documented. This study was therefore designed to evaluate the effects of a reference DEP extract (DEPe) on human M Phi polarization. Human blood monocytes-derived M Phi were incubated with IFN gamma +LPS or IL-4 to obtain M1 and M2 subtypes, respectively; a 24 h exposure of polarizing M Phi to 10 mu g/ml DEPe was found to impair expression of some macrophagic M1 and M2 markers, without however overall inhibition of M1 and M2 polarization processes. Notably, DEPe treatment increased the secretion of the M1 marker IL-8 and the M2 marker IL-10 in both M Phi subtypes, whereas it reduced lipopolysaccharide-induced IL-6 and IL-12p40 secretion in M1 M Phi . In M2 M Phi , DEPe exposure led to a reduction of CD200R expression and of CCL17, CCL18 and CCL22 secretion, associated with a lower chemotaxis of CCR4-positive cells. DEPe activated the Nrf2 and AhR pathways and induced expression of their reference target genes such as Hmox-1 and cytochrome P-4501B1 in M1 and M2 M Phi . Nrf2 or AhR silencing through RNA interference prevented DEPe-related down-regulation of IL-6. AhR silencing also inhibited the down-secretion of IL-12p40 and CCL18 in M1- and M2-DEPe-exposed M Phi , respectively. DEPs are therefore likely to alter expression of some M1 and M2 markers in an AhR- and Nrf2-dependent manner; such regulations may contribute to deleterious immune effects of atmospheric DEP.