The role of oxidative stress in the pathogenesis and treatment of asthma

Dozor, Allen J.

doi:10.1111/j.1749-6632.2010.05562.x

Cited by 99 publications

(74 citation statements)

References 39 publications

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“…In this regard, we might speculate that MC hyperresponsiveness may be associated with abrupt and intense exposure to AhR ligands commonly spread in industrialized countries (e.g., dioxins, airborne pollutants, tryptophan-rich dietary compounds), which may correlate with the onset of allergy and allergy-related pathologies in young individuals who encounter these compounds together with the allergen for the first time (31). Strikingly, FICZ-dependent formation of ROS observed in our experiments would also be in accordance and contribute to the enhancement of the overall inflammatory acute response observed in young allergic patients (32). Alternatively, repetitive exposure to AhR-ligand pollutants could suppress MC degranulation and attenuate the allergic response in favor of other types MCmediated responses (e.g., inflammatory responses) by directly acting on AhR-mediated MC responsiveness (10).…”

Section: Discussionsupporting

confidence: 78%

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

Sibilano

Frossi

Calvaruso

et al. 2012

The Journal of Immunology

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The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics as well as physiological ligands. These compounds may modulate inflammatory responses and contribute to the rising prevalence of allergic diseases observed in industrialized countries. Mast cells (MCs), located within tissues at the boundary of the external environment, represent a potential target of AhR ligands. In this study, we report that murine and human MCs constitutively express AhR, and its activation by the high-affinity ligand 6-formylindolo[3,2-b]carbazole (FICZ) determines a boost in degranulation. On the contrary, repeated exposure to FICZ inhibits MC degranulation. Accordingly, histamine release, in an in vivo passive systemic anaphylactic model, is exacerbated by a single dose and is attenuated by repetitive stimulation of AhR. FICZ-exposed MCs produce reactive oxygen species and IL-6 in response to cAMP-dependent signals. Moreover, AhR-activated MCs produce IL-17, a critical player in chronic inflammation and autoimmunity, suggesting a novel pathway for MC activation in the pathogenesis of these diseases. Indeed, histological analysis of patients with chronic obstructive pulmonary disease revealed an enrichment in AhR/IL-6 and AhR/IL-17 double-positive MCs within bronchial lamina propria. Thus, tissue-resident MCs could translate external chemical challenges through AhR by modulating allergic responses and contributing to the generation of inflammation-related diseases.

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Section: Discussionsupporting

confidence: 78%

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

Sibilano

Frossi

Calvaruso

et al. 2012

The Journal of Immunology

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“…We tested our hypothesis that GRP mediates asthma by using two distinct mouse models of AHR and airways inflammation: ovalbumin (OVA)-induced AHR and eosinophilic inflammation as a model for allergic asthma, and ozone-induced AHR and neutrophilic inflammation as a model for asthma triggered by air pollution (33). Asthma is a human disease defined functionally (physiologically) as intermittent airway obstruction.…”

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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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“…Asthma occurrence is dependent on the relationship between antioxidant and inflammatory genes [9]. Higher levels of oxidative stress overwhelm antioxidant defenses and lead to the induction of many pro-inflammatory factors including tumor necrosis factor α (TNF-α) [10].…”

Section: Original Papersmentioning

confidence: 99%

Gene Polymorphisms of Tumor Necrosis Factor Alpha and Antioxidant Enzymes in Bronchial Asthma

Despotović¹,

Stoimenov²,

Stanković³

et al. 2015

Adv Clin Exp Med

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Background. Bronchial asthma is an inflammatory disease resulting from a combination of genetic and environmental factors. Single nucleotide polymorphisms in the regulatory regions of cytokine and antioxidant enzyme genes may affect cytokine production and enzyme activity, and thus play a contributory role in asthma pathogenesis. Objectives. The aim of this study was to examine the association of manganese superoxide dismutase (MnSOD) Ala16Val, catalase (CAT) A-21T and tumor necrosis factor alpha (TNF-α) G-308A polymorphisms with bronchial asthma. Material and Methods. A total of 79 patients with asthma and 95 healthy controls were screened for MnSOD Ala16Val, CAT A-21T and TNF-α G-308A polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

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The role of oxidative stress in the pathogenesis and treatment of asthma

Cited by 99 publications

References 39 publications

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

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

Gene Polymorphisms of Tumor Necrosis Factor Alpha and Antioxidant Enzymes in Bronchial Asthma

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