Roles of reactive oxygen species and heme oxygenase-1 in modulation of alveolar macrophage-mediated pulmonary immune responses to Listeria monocytogenes by diesel exhaust particles.
Diesel exhaust particles (DEP) have been shown to suppress alveolar macrophage (AM)-mediated pulmonary immune responses to Listeria monocytogenes in vivo. In this study, effects of DEP-derived reactive oxygen species (ROS) and heme oxygenase (HO)-1 on AM-mediated immune responses to L. monocytogenes were investigated. Brown Norway rats were intratracheally inoculated with 100,000 L. monocytogenes, and AM were isolated at 7 days post-infection. Exposure to DEP or their organic extract (eDEP), but not the washed DEP (wDEP) or carbon black, increased intracellular ROS and HO-1 expression in AM. Induction of ROS and HO-1 by eDEP was partially reversed by alpha-naphthoflavone, a cytochrome P450 1A1 inhibitor, and totally blocked by N-acetylcysteine. In addition, exposure to eDEP, but not wDEP, inhibited lipopolysacchride-stimulated secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-12 (IL-12), but augmented production of IL-10 by AM. Kinetic studies showed that modulation of cytokines by eDEP was preceded by ROS and HO-1 induction. Furthermore, pretreatment of AM with superoxide dismutase (SOD) or zinc protoporphrin IX (Znpp), which attenuated eDEP-induced HO-1 expression/activity, substantially inhibited eDEP effect on IL-10. Finally, direct stimulation with pyrogallol (PYR), a superoxide donor, upregulated HO-1 and IL-10 but decreased secretion of IL-12 in L. monocytogenes-infected AM. These results show that DEP, through eDEP-mediated ROS, induce HO-1 expression and IL-10 production and at the same time inhibit AM production of TNF-alpha and IL-12 to dampen the host immune responses. The results also suggest that HO-1 may play an important role in regulating production of IL-10 by DEP-exposed and L. monocytogenes-infected AM.
Yin
Xuejun J
XJ
School of Pharmacy, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506 , USA.
Ma
Jane Y C
JY
Antonini
James M
JM
Castranova
Vincent
V
Ma
Joseph K H
JK
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004338:Drug Combinations; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D011524:Protoporphyrins / Q000494:pharmacology; D011748:Pyrogallol / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D001335:Vehicle Emissions / Q000633:toxicity*
D001571:Benzoflavones; D016207:Cytokines; D004338:Drug Combinations; D008070:Lipopolysaccharides; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D011748:Pyrogallol; C017803:zinc protoporphyrin; C011512:alpha-naphthoflavone; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D000111:Acetylcysteine