Diesel exhaust particles increase LPS-stimulated COX-2 expression and PGE2 production in human monocytes

Abstract

Little is known about health effects of ultrafine particles (UFP) found in ambient air, but much of their action may be on cells of the lung, including cells of the monocyte/macrophage lineage. We have analyzed the effects of diesel exhaust particles (DEP; SRM1650a) on human monocytes in vitro. DEP, on their own, had little effect on cyclooxygenase (COX)-2 gene expression in the Mono Mac 6 cell line. However, when cells were preincubated with DEP for 1 h, then stimulation with the Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) induced an up-to fourfold-higher production of COX-2 mRNA with an average twofold increase. This costimulatory effect of DEP led to enhanced production of COX-2 protein and to increased release of prostaglandin E(2) (PGE(2)). The effect was specific in that tumor necrosis factor gene expression was not enhanced by DEP costimulation. Furthermore, costimulation with the TLR2 ligand Pam3Cys also led to enhanced COX-2 mRNA. DEP and LPS showed similar effects on COX-2 mRNA in primary blood mononuclear cells, in highly purified CD14-positive monocytes, and in monocyte-derived macrophages. Our data suggest that UFP such as DEP may exert anti-inflammatory effects mediated by enhanced PGE(2) production.

Immune Complex/Ig Negatively Regulate TLR4-Triggered Inflammatory Response in Macrophages through FcγRIIb-Dependent PGE2 Production

“…It has been reported that proinflammatory stimuli, such as LPS or TNF-␣, can stimulate macrophages to produce PGE 2 for feedback negative regulation of inflammatory responses (25,26), so we observed whether LPS could affect IC-induced PGE 2 production. We incubated peritoneal macrophages with IC, LPS, or IC plus LPS for 12 h and found that LPS alone could induce PGE 2 produced from macrophages.…”

Pro-inflammatory potential of wood smoke and traffic-derived particles in a monocytic cell line

“…Monocytes have also been suggested to accumulate in the alveoli after repeated exposure to particulate matter, to assist with particle clearance (Goto et al, 2004b). In vitro experiments provide further support for a role of monocytes in lung inflammation, since particle exposure has been found to generate oxidative stress and induce release of pro-inflammatory mediators in monocytes (Monn and Becker, 1999;Becker et al, 2002;Hofer et al, 2004). Since monocytes are recruited to inflamed alveoli (Maus et al, 2001), and may play a role in clearing foreign material such as particles (Goto et al, 2004b), the monocytic cell line THP-1 was used as target for particles in the present study.…”

SWCNT suppress inflammatory mediator responses in human lung epithelium in vitro

“…Therefore, evaluating the effects of SWCNT exposure on rh-TNF-α-or LPS-induced cells may give an indication of whether the presence of an infection may give rise to increased SWCNT toxicity compared to normal, unstimulated cells or whether the presence of SWCNT can modulate inflammatory responses during infections. It has also been proposed that bacterial products such as LPS associated with particles may have stimulatory effects on the cytokine production of macrophages and maybe also epithelial cells [Becker et al, 2005a;Hofer et al, 2004]. While epithelial cells only slightly respond to LPS when compared to macrophages, they do express TLR receptors and have been shown to release IL-8 in response to treatment with different kinds of LPS with LPS from…”

“…There are also reports of diesel particles having suppressive or synergistic effects on LPS-induced cytokine production [Amakawa et al, 2003;Hofer et al, 2004;Yang et al, 2001].…”