Ambient Ozone Primes Pulmonary Innate Immunity in Mice

Hollingsworth, John W.; Maruoka, Shuichiro; Li, Zhuowei; Potts, Erin N.; Brass, David M.; Garantziotis, Stavros; Fong, Alan M.; Foster, W. Michael; Schwartz, David A.

doi:10.4049/jimmunol.179.7.4367

Cited by 68 publications

(59 citation statements)

References 54 publications

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“…S1), representing 157-271% increased airway resistance over filtered air (FA) controls at baseline. This model has been used successfully in multiple laboratories (34,37,38). A recent report (39) showed the kinetics (6-48 h after exposure) of inflammation and robust AHR development to methacholine (MCh) 24 h after O 3 .…”

Section: Resultsmentioning

confidence: 99%

RETRACTED: Gastrin-releasing peptide blockade as a broad-spectrum anti-inflammatory therapy for asthma

Zhou¹,

Potts

Cuttitta

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Gastrin-releasing peptide (GRP) is synthesized by pulmonary neuroendocrine cells in inflammatory lung diseases, such as bronchopulmonary dysplasia (BPD). Many BPD infants develop asthma, a serious disorder of intermittent airway obstruction. Despite extensive research, early mechanisms of asthma remain controversial. The incidence of asthma is growing, now affecting >300 million people worldwide. To test the hypothesis that GRP mediates asthma, we used two murine models: ozone exposure for air pollution-induced airway hyperreactivity (AHR), and ovalbumin (OVA)-induced allergic airway disease. BALB/c mice were given small molecule GRP blocking agent 77427, or GRP blocking antibody 2A11, before exposure to ozone or OVA challenge. In both models, GRP blockade abrogated AHR and bronchoalveolar lavage (BAL) macrophages and granulocytes, and decreased BAL cytokines implicated in asthma, including those typically derived from Th1 (e.g., IL-2, TNFα), Th2 (e.g., IL-5, IL-13), Th17 (IL-17), macrophages (e.g., MCP-1, IL-1), and neutrophils (KC = IL-8). Dexamethasone generally had smaller effects on all parameters. Macrophages, T cells, and neutrophils express GRP receptor (GRPR). GRP blockade diminished serine phosphorylation of GRPR with ozone or OVA. Thus, GRP mediates AHR and airway inflammation in mice, suggesting that GRP blockade is promising as a broad-spectrum therapeutic approach to treat and/or prevent asthma in humans.

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Section: Resultsmentioning

confidence: 99%

RETRACTED: Gastrin-releasing peptide blockade as a broad-spectrum anti-inflammatory therapy for asthma

Zhou¹,

Potts

Cuttitta

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Furthermore, many epidemiological and experimental studies have shown that individuals with pre-existing inflammatory conditions are more prone to the adverse effects of environmental injury. [15][16][17] Indeed, aggravation of pre-existing inflammation has been documented after exposure to particulate air pollution and various types of nanoparticles. [18][19][20][21] This study was designed to investigate the inflammationmodulating effects of CeO 2 nanoparticles in human peripheral blood monocytes at noncytotoxic exposure concentrations.…”

Section: Introductionmentioning

confidence: 99%

Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

Hussain¹,

Al-Nsour²,

Rice³

et al. 2012

IJN

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Background: Cerium dioxide (CeO 2 ) nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO 2 nanoparticles. We investigated the inflammation-modulating effects of CeO 2 nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes. Methods: CD14+ cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 µg/mL of CeO 2 nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL) prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10. Results: CeO 2 nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter), zeta potential analysis (−14 mV), and transmission electron microscopy (irregular-shaped particles). Transmission electron microscopy of CD14 + cells exposed to CeO 2 nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO 2 nanoparticletreated cells and control cells at noncytotoxic doses. No significant effects of CeO 2 nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO 2 nanoparticles followed by lipopolysaccharide exposure. Conclusion: CeO 2 nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects.

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“…In a mouse model, preexposure to nonlethal concentrations of ozone was shown to prime the innate immune system, resulting in an increased Toll-like receptor-4-mediated response to subsequent stimulation with inhaled endotoxin (10). Chronic environmental ozone exposure in humans may have a similar effect, enhancing Toll-like receptor-4-mediated inflammatory signaling in the lung.…”

Section: It's In the Air We Breathementioning

confidence: 86%