Neurogenic mechanisms in bronchial inflammatory diseases

Groneberg, David A.; Quarcoo, David; Frossard, Nelly; Fischer, Axel

doi:10.1111/j.1398-9995.2004.00665.x

Cited by 153 publications

(109 citation statements)

References 144 publications

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“…Asthmatic exacerbations can be triggered by allergens, pollution, or infections (2), leading to structural remodeling (9) involving mast cells, eosinophils, and Th2 lymphocytes (CD4 + T cells) (10), which produce cytokines and mediators (11). Neuropeptides from sensory nerve fibers, such as substance P, can elicit "neurogenic inflammation" (12), mainly linked to neutrophilic inflammation and vascular leakage, possibly contributing to bronchoconstriction (13,14). Cigarette smoke elicits nonspecific AHR to substance P in guinea pigs, which is of unclear significance to asthma in humans (15).…”

mentioning

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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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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“…Over the last decades, evidence has mounted for bi-directional feedback between immunogenic and neurogenic mechanisms in airway inflammation (6,7). Neuronal activation causes pain and irritation, neurogenic inflammation, mucus secretion, and reflex responses, such as cough, sneezing, and bronchoconstriction (8,9). Members of the transient receptor potential (TRP) superfamily of ion channels play a key role in the response of sensory neurons to inflammatory mediators (10)(11)(12).…”

mentioning

confidence: 99%

A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma

Caceres

Brackmann²,

Elia³

et al. 2009

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

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386

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Asthma is an inflammatory disorder caused by airway exposures to allergens and chemical irritants. Studies focusing on immune, smooth muscle, and airway epithelial function revealed many aspects of the disease mechanism of asthma. However, the limited efficacies of immune-directed therapies suggest the involvement of additional mechanisms in asthmatic airway inflammation. TRPA1 is an irritant-sensing ion channel expressed in airway chemosensory nerves. TRPA1-activating stimuli such as cigarette smoke, chlorine, aldehydes, and scents are among the most prevalent triggers of asthma. Endogenous TRPA1 agonists, including reactive oxygen species and lipid peroxidation products, are potent drivers of allergen-induced airway inflammation in asthma. Here, we examined the role of TRPA1 in allergic asthma in the murine ovalbumin model. Strikingly, genetic ablation of TRPA1 inhibited allergen-induced leukocyte infiltration in the airways, reduced cytokine and mucus production, and almost completely abolished airway hyperreactivity to contractile stimuli. This phenotype is recapitulated by treatment of wild-type mice with HC-030031, a TRPA1 antagonist. HC-030031, when administered during airway allergen challenge, inhibited eosinophil infiltration and prevented the development of airway hyperreactivity. Trpa1 ؊/؊ mice displayed deficiencies in chemically and allergen-induced neuropeptide release in the airways, providing a potential explanation for the impaired inflammatory response. Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving asthmatic airway inflammation following inhaled allergen challenge. TRPA1 may represent a promising pharmacological target for the treatment of asthma and other allergic inflammatory conditions. airway hyperreactivity ͉ TRP channel ͉ TRPA1

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“…In turn, NK-1 receptors have been shown to be present in numerous lung structures, including the airway epithelium from the bronchi to the alveoli of guinea pigs and humans (16,17). Substance P, via NK-1 receptors, plays a role in regulating airway blood flow, airway smooth muscle responses, airway inflammation (18), and epithelial migration and proliferation of cells, including tracheal epithelial cells, after injury (19)(20)(21). Substance P induces superoxide production in neutrophils, is a chemotactic agent for human neutrophils, and primes neutrophils for response to other activating agents (22)(23)(24).…”

mentioning

confidence: 99%

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Oslund¹,

Hyde

Putney³

et al. 2008

Am J Respir Cell Mol Biol

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We investigated the importance of neurokinin (NK)-1 receptors in epithelial injury and repair and neutrophil function. Conscious Wistar rats were exposed to 1 ppm ozone or filtered air for 8 hours, followed by an 8-hour postexposure period. Before exposure, we administered either the NK-1 receptor antagonist, SR140333, or saline as a control. Ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, whole mounts of airway dissected lung lobes were immunostained for 5-bromo-29-deoxyuridine, a marker of epithelial proliferation. Both ethidium homodimer and 5-bromo-29-deoxyuridine-positive epithelial cells were quantified in specific airway generations. Rats treated with the NK-1 receptor antagonist had significantly reduced epithelial injury and epithelial proliferation compared with control rats. Sections of terminal bronchioles showed no significant difference in the number of neutrophils in airways between groups. In addition, staining ozone-exposed lung sections for active caspase 3 showed no apoptotic cells, but ethidium-positive cells colocalized with the orphan nuclear receptor, Nur77, a marker of nonapoptotic, programmed cell death mediated by the NK-1 receptor. An immortalized human airway epithelial cell line, human bronchial epithelial-1, showed no significant difference in the number of oxidant stresspositive cells during exposure to hydrogen peroxide and a range of SR140333 doses, demonstrating no antioxidant effect of the receptor antagonist. We conclude that activation of the NK-1 receptor during acute ozone inhalation contributes to epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

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Neurogenic mechanisms in bronchial inflammatory diseases

Cited by 153 publications

References 144 publications

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

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

A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

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