Interleukin-8 induction by the environmental contaminant benzo(a)pyrene is aryl hydrocarbon receptor-dependent and leads to lung inflammation

Podechard, Normand; Lecureur, Valérie; Ferrec, Eric Le; Guénon, Isabelle; Sparfel, Lydie; Gilot, David; Gordon, John; Lagente, Vincent; Fardel, Olivier

doi:10.1016/j.toxlet.2008.01.006

Cited by 116 publications

(74 citation statements)

References 41 publications

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“…4), used here as a convenient normal cell model for investigating AhR-related regulatory pathways (Komura et al, 2001;NЈDiaye et al, 2006;Monteiro et al, 2007;Podechard et al, 2008). TCDD, used as a positive control, similarly induced expression of ITG␤7, CYP1B1, and IL-8 (Fig.…”

Section: Resultsmentioning

confidence: 92%

Activation of the Aryl Hydrocarbon Receptor by the Calcium/Calmodulin-Dependent Protein Kinase Kinase Inhibitor 7-Oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic Acid (STO-609)

Monteiro

Gilot²,

Langouët³

et al. 2008

Drug Metab Dispos

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Section: Resultsmentioning

confidence: 92%

Activation of the Aryl Hydrocarbon Receptor by the Calcium/Calmodulin-Dependent Protein Kinase Kinase Inhibitor 7-Oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic Acid (STO-609)

Monteiro

Gilot²,

Langouët³

et al. 2008

Drug Metab Dispos

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“…These concentrations are about 1000-fold less than those previously used to demonstrate cytokine responses to single PAHs. [19,20] Moreover, these mid-polar (20% DCM in n-hexane) SPE fractions did not induce significant cellular effects (Figs. 5 and 7), and accordingly the content of these groups of compounds did not correlate with the toxicological effects in the linear regression analysis.…”

Section: Role Of Alkanes Pahs and Their Mildly Polar Derivativesmentioning

confidence: 95%

“…[1,18] However, exposure to high concentrations of various single PAHs, as well as nitro-and amino-PAH derivatives, has been reported to induce additional pro-inflammatory responses, both in vivo and in vitro. [19,20] Such effects have been linked to both ligand binding and activation of the aryl hydrocarbon receptor, antagonist properties, as well as to the formation of reactive electrophilic metabolites during the PAH metabolism. [21,22] Although this indicates that PAHs may be important for inflammatory responses, their contribution to the pro-inflammatory effects of DEPs and other combustion particles, to our knowledge, has not yet been clarified.…”

Section: Introductionmentioning

confidence: 99%

The occurrence of polycyclic aromatic hydrocarbons and their derivatives and the proinflammatory potential of fractionated extracts of diesel exhaust and wood smoke particles

Totlandsdal

Øvrevik

Cochran

et al. 2013

Journal of Environmental Science and Health, Part A

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Exposure to combustion emissions, including diesel engine exhaust and wood smoke particles (DEPs and WSPs), has been associated with inflammatory responses. To investigate the possible role of polycyclic aromatic hydrocarbons (PAHs) and PAH-derivatives, the DEPs and WSPs methanol extracts were fractionated by solid phase extraction (SPE), and the fractions were analyzed for more than ∼120 compounds. The pro-inflammatory effects of the fractionated extracts were characterized by exposure of bronchial epithelial lung cells (BEAS-2B). Both native DEPs and WSPs caused a concentration-dependent increase in IL-6 and IL-8 release and cytotoxicity. This is consistent with the finding of a rather similar total content of PAHs and PAH-derivatives. Yet, the samples differed in specific components, suggesting that different species contribute to the toxicological response in these two types of particles. The majority of the IL-6 release and cytotoxicity was induced upon exposure to the most polar (methanol) SPE fraction of extracts from both samples. In these fractions hydroxy-PAHs, carboxy-PAHs were observed along with nitro-amino-PAHs in DEP. However, the biological effects induced by the polar fractions could not be attributed only to the occurrence of PAH-derivatives. The present findings indicate a need for further characterization of organic extracts, beyond an extensive analysis of commonly suspected PAH and PAH-derivatives.

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“…Town, F. Li, W. Li, X. Zhang, and J. Gordon, submitted for publication), ischemia-reperfusion injury (X. Zhao, J. Town, A. Yang, X. Zhang, G. Sawicki, and J. Gordon, submitted for publication), and environmental pollutant-induced lung injury (33). Although we know in airway endotoxemia that bG31P treatments reduce neutrophil infiltration of the airways, it remains possible that neutrophils marginate in the pulmonary vasculature under the influence of the inflammatory mediators expressed in this compartment and are activated in situ.…”

Section: G31p Blocks Airway Endotoxemia-induced Acute Lung Inflammationmentioning

confidence: 99%

ELR-CXC Chemokine Receptor Antagonism Targets Inflammatory Responses at Multiple Levels

Zhao

Town

et al. 2009

The Journal of Immunology

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The ELR-CXC chemokines play important roles in neutrophilic inflammation. We report in this study that a fully human ELR-CXC chemokine antagonist that we have generated, CXCL8(3–72)K11R/G31P (G31P), has potent anti-inflammatory effects that arise through its actions at multiple levels. G31P inhibited CXCL8-induced chemotactic responses and intracellular Ca2+ flux in CXCR1-transfected HEK cells and neutrophils, and responses of neutrophils to CXCR2-exclusive ligands. G31P desensitized heterologous G protein-coupled receptors on neutrophils, 52–86% reducing their Ca2+ flux and chemotactic responses to leukotriene B4, C5a, and the bacterial tripeptide fMLP. G31P also 60–90% blocked neutrophil chemotactic responses to mediators present in 10 of 12 sputum samples from cystic fibrosis or bronchiectasis subjects with bacterial pneumonia. Moreover, whereas A549 bronchial epithelial cells (which expressed CXCR1) secreted ≈29,000 pg/ml CXCL8 in response to in vitro endotoxin challenge, G31P reduced this response by up to 98%, presumably by interrupting an autocrine inflammatory loop. The anti-inflammatory effects of G31P extended also to reversing the antiapoptotic influence of ELR-CXC chemokines on neutrophils. That these effects were relevant in vivo was confirmed in a guinea pig model of airway endotoxemia, wherein the human form of G31P >95% blocked neutrophil infiltration into and activation within the airways, as determined by airway levels of the neutrophil primary, secondary, and tertiary granule markers myeloperoxidase, lactoferrin, and matrix metalloproteinase-9, respectively, and the epithelial cell marker matrix metalloproteinase-2. These data suggest that the beneficial effects of ELR-CXC chemokine antagonism arise through effects that occur at multiple levels, including epithelial cells, neutrophils, and alternate G protein-coupled receptors.

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Interleukin-8 induction by the environmental contaminant benzo(a)pyrene is aryl hydrocarbon receptor-dependent and leads to lung inflammation

Cited by 116 publications

References 41 publications

Activation of the Aryl Hydrocarbon Receptor by the Calcium/Calmodulin-Dependent Protein Kinase Kinase Inhibitor 7-Oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic Acid (STO-609)

Activation of the Aryl Hydrocarbon Receptor by the Calcium/Calmodulin-Dependent Protein Kinase Kinase Inhibitor 7-Oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic Acid (STO-609)

The occurrence of polycyclic aromatic hydrocarbons and their derivatives and the proinflammatory potential of fractionated extracts of diesel exhaust and wood smoke particles

ELR-CXC Chemokine Receptor Antagonism Targets Inflammatory Responses at Multiple Levels

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