Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: Essential role of GM-CSF☆☆☆

Ohta, Ken; Yamashita, Naomi; Tajima, Makoto; Miyasaka, Takashi; Nakano, Junichi; Nakajima, Mikio; Ishii, Akira; Horiuchi, Tadashi; Mano, Kenji; Miyamoto, Tomofumi

doi:10.1016/s0091-6749(99)70084-9

Cited by 104 publications

(73 citation statements)

References 39 publications

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“…Additional evidence supporting the role of oxidative stress in PM-induced airway inflammation comes from animal studies [56][57][58]. For example, intratracheal instillation of DEP leads to increased PMN infiltration, increased mucus, nitric oxide production, and increased airway hyperreactivity (AHR) in mice, all of which play important role in the pathogenesis of asthma [59][60][61][62][63][64][65]. These effects can be suppressed by pre-treating the animals with SOD or with the nitric oxide synthase inhibitors [60,63,64].…”

Section: The Impact Of Particulate Pollutants On Asthmamentioning

confidence: 99%

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

Xia

Nel

2008

Free Radical Biology and Medicine

802

529

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Ambient particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is the exacerbation of inflammation, especially in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is the generation of oxidative stress by its chemical compounds and metals. Cellular responses to PM-induced oxidative stress include activation of antioxidant defense, inflammation, and toxicity. The pro-inflammatory effect of PM in the lung is characterized by increased cytokine/chemokine production and adhesion molecule expression. Moreover, there is evidence that ambient PM can act as an adjuvant for allergic sensitization, which raises the possibility that long-term PM exposure may lead to increased prevalence of asthma. In addition to ambient PM, rapid expansion of nanotechnology has introduced the potential that engineered NP may also become airborne and may contribute to pulmonary diseases by novel mechanisms that could include oxidant injury. Currently, little is known about the potential adverse health effect of these particles. In this communication, the mechanisms by which particulate pollutants, including ambient PM and engineered NP, exert their adverse effects through the generation of oxidative stress and the impacts of oxidant injury in the respiratory tract will be reviewed. The importance of cellular antioxidant and detoxification pathways in protecting against particle-induced lung damage will also be discussed.

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Section: The Impact Of Particulate Pollutants On Asthmamentioning

confidence: 99%

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

Xia

Nel

2008

Free Radical Biology and Medicine

802

529

View full text Add to dashboard Cite

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“…Administration of a GM-CSF-neutralizing mAb attenuated allergic airway inflammation in a murine model of asthma, significantly reducing airway hyperresponsiveness (AHR), airway eosinophilia, and pulmonary inflammation (9). In a study on inhalation of diesel exhaust particles in mice, AHR and Clara cell hyperplasia were attenuated by anti-GM-CSF Ab (10). In a report on intranasal exposure to house dust mite, administration of a GM-CSF-neutralizing mAb markedly reduced inflammatory responses in the lung and spleen and resulted in reduced Th2 effector cells and airway eosinophilia (11).…”

mentioning

confidence: 99%

Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation

Rolph

Hansbro

et al. 2008

The Journal of Immunology

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GM-CSF plays an important role in inflammation by promoting the production, activation, and survival of granulocytes and macrophages. In this study, GM-CSF knockout (GM-CSF−/−) mice were used to investigate the role of GM-CSF in a model of allergic airway inflammation. In allergic GM-CSF−/− mice, eosinophil recruitment to the airways showed a striking pattern, with eosinophils present in perivascular areas, but almost completely absent in peribronchial areas, whereas in wild-type mice, eosinophil infiltration appeared in both areas. In the GM-CSF−/− mice, mucus production in the airways was also reduced, and eosinophil numbers were markedly reduced in the bronchoalveolar lavage (BAL)3 fluid. IL-5 production was reduced in the lung tissue and BAL fluid of GM-CSF−/− mice, but IL-4 and IL-13 production, airway hyperresponsiveness, and serum IgE levels were not affected. The presence of eosinophils in perivascular but not peribronchial regions was suggestive of a cell migration defect in the airways of GM-CSF−/− mice. The CCR3 agonists CCL5 (RANTES) and CCL11 (eotaxin-1) were expressed at similar levels in GM-CSF−/− and wild-type mice. However, IFN-γ mRNA and protein were increased in the lung tissue and BAL fluid in GM-CSF−/− mice, as were mRNA levels of the IFN-γ-inducible chemokines CXCL9 (Mig), CXCL10 (IP-10), and CXCL11 (I-Tac). Interestingly, these IFN-γ-inducible chemokines are natural antagonists of CCR3, suggesting that their overproduction in GM-CSF−/− mice contributes to the lack of airway eosinophils. These findings demonstrate distinctive abnormalities to a model of allergic asthma in the absence of GM-CSF.

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“…Moreover, GM-CSF stimulates activation of the 5-lipoxygenase pathway (19). In addition, murine models of asthma and dieselinduced hyper-responsiveness have demonstrated an association between epithelial cell-derived GM-CSF and airway hyper-responsiveness (20,21).…”

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confidence: 99%

Regulation of Expression of Granulocyte-Macrophage Colony-Stimulating Factor in Human Bronchial Epithelial Cells: Roles of Protein Kinase C and Mitogen-Activated Protein Kinases

Reibman

Talbot

Hsu

et al. 2000

The Journal of Immunology

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GM-CSF has a major role in the immune and inflammatory milieu of the airway. Airway epithelial cells (AEC) are among the first targets of environmental stimuli and local cytokines, in response to which they can produce GM-CSF. The regulation of GM-CSF is only minimally understood in AEC. We hypothesized that GM-CSF expression in AEC would result from activation of protein kinase C (PKC) and subsequent activation of the extracellular signal-regulated kinase (MAPKerk1/2) pathway, so we investigated signal transduction pathways in human primary culture bronchial epithelial cells (HBECs). TNF-α, IL-1β, and PMA induced the release of GM-CSF in HBECs. The robust response to PMA was not detected in SV40 adenovirus-transformed normal human bronchial epithelial cells (BEAS-2B). PMA and TNF-α stimulation of GM-CSF required activation of PKC (inhibition by staurosporine and bisindolylmaleimide I). GM-CSF expression was up-regulated by a nonphorbol PKC activator, but not by an inactive PMA analogue. PMA-induced GM-CSF production in HBECs did not require a Ca2+ ionophore and was not inhibited by cyclosporin A. Activation of MAPKerk1/2 via PKC was associated with and was required for GM-CSF production induced by PMA and TNF-α. The data demonstrate regulation of GM-CSF in HBECs by PKC pathways converging on the MAPKerk1/2 pathway and further define cell-specific regulation critical for local airway responses.

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Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: Essential role of GM-CSF☆☆☆

Cited by 104 publications

References 39 publications

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation

Regulation of Expression of Granulocyte-Macrophage Colony-Stimulating Factor in Human Bronchial Epithelial Cells: Roles of Protein Kinase C and Mitogen-Activated Protein Kinases

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