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

Journal of Leukocyte Biology

Joachim Heyder⁴  Löms Ziegler-Heitbrock¹  Konrad L. Maier⁴  Ellen Bitterle⁵  Marion Frankenberger²  Ingrid Beck-Speier⁴  Thomas P. J. Hofer³ 

[1] Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and Division of Immunology, University of Leicester, United Kingdom Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and Division of Immunology, University of Leicester, United Kingdom Division of Immunology, University of Leicester, United Kingdom Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and Division of Immunology, University of Leicester, United Kingdom;Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and;GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; and GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; Clinical Cooperation Group Inflammatory Lung Diseases, GSF-Institute for Inhalation Biology and Asklepios Fachkliniken Muenchen-Gauting, Gauting, Germany; andGSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany;GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; GSF Focus-Network Aerosols and Health; GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; GSF Focus-Network Aerosols and Health; GSF Focus-Network Aerosols and Health; GSF National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg, Germany; GSF Focus-Network Aerosols and Health;

关键词: cyclooxygenase 2;    DEP;    inflammation;    LPS;    Pam3Cys;    Mono Mac 6;   

DOI  :  10.1189/jlb.0803387

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 E2 (PGE2). 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 PGE2 production.

【 授权许可】

Unknown