Diisocyanate asthma: clinical aspects and immunopathogenesis

Redlich, Carrie A.; Karol, Meryl H.

doi:10.1016/s1567-5769(01)00174-6

Cited by 138 publications

(97 citation statements)

References 76 publications

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“…Numerous studies have investigated the role of the well-characterized asthmogen, toluene 2,4-diisocyanate (TDI; which is now being phased out of commercial use) in allergic disease (Johnson et al, 2007). Studies conducted in humans exposed to diisocyanates and animal models suggest that a mixed T H 1/T H 2 immune response is associated with TDI exposure with T H 2 cytokines, including interleukin (IL)-4 and IL-5, as well as T H 1 cytokines, such as interferon (IFN)-g, being identified in the respiratory mucosa of workers following exposure (Maestrelli et al, 1995(Maestrelli et al, , 1997Redlich & Karol, 2002).…”

Section: Introductionmentioning

confidence: 99%

Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Anderson

Beezhold

Lukomska

et al. 2013

Journal of Immunotoxicology

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Allergic disease is an important occupational health concern, with work-related asthma and allergic contact dermatitis being the most frequently diagnosed occupational illnesses. Diisocyanates, particularly toluene 2,4-diisocyanate (TDI), have been the leading cause of occupational asthma for many years. Understanding the mechanisms behind allergic disease is critical for treatment and prevention. Recently, the study of post-transcriptional regulation by microRNAs (miRNA) has shed light on mechanisms of allergic disease. The present studies report the expression of miRNA during the sensitization phase of an allergic response to TDI in a murine model. Female BALB/c mice were dermally exposed to TDI (0.1-15% [v/v]) or vehicle. RNA was isolated from superficial parotid lymph nodes at timepoints between 1 h and 15 days post-exposure and then miRNA expression was analyzed using array and real-time quantitative PCR analysis. Consistent changes in miRNA expression were identified for miR-21, miR-22, miR-27b, miR-31, miR-126, miR-155, miR-210, and miR-301a. Following TDI exposure, peak expression was observed by Day 4 for the majority of miRNA evaluated with trends in expression correlated to exposure concentration. Confirmed and predicted targets were identified using Diana-microT, miRanda, miRwalk, and Targetscan algorithms. Evaluation of mRNA expression of cytokine and transcription factor targets suggests that miRNA may have a central role early in TDI sensitization. Understanding the role of these miRNA and their specific mechanism of action in sensitization to TDI may provide pertinent information for the identification of other chemical sensitizers while also contributing to the treatment and prevention of allergic disease.

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Section: Introductionmentioning

confidence: 99%

Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Anderson

Beezhold

Lukomska

et al. 2013

Journal of Immunotoxicology

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“…Asthma studies in humans exposed to diisocyanates and animal models suggest that T lymphocytes are critical to disease and orchestrate a mixed Th1/Th2 immune response (6). Diisocyanate-specific T cell clones, Th2 cytokines, including IL-4 and IL-5, as well as Th1 cytokines, such as IFN-␥, have been identified in the respiratory mucosa of workers following exposure to diisocyanates (7)(8)(9). Important roles for Th2 and Th1 cytokines, as well as specific Abs, have been confirmed using transgenic approaches in animal models of diisocyanate asthma (10,11).…”

mentioning

confidence: 96%

Inhalation of Toluene Diisocyanate Vapor Induces Allergic Rhinitis in Mice

Johnson

Yücesoy

Reynolds

et al. 2007

The Journal of Immunology

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Diisocyanates are the leading cause of occupational asthma, and epidemiological evidence suggests that occupational rhinitis is a comorbid and preceding condition in patients who develop asthma. The goal of the present studies was to develop and characterize a murine model of toluene diisocyanate (TDI)-induced rhinitis. Female C57BL/6 mice were exposed to workplace-relevant concentrations of TDI vapor via inhalation for 4 h/day for 12 days with or without a 2-wk rest period and TDI challenge. Mice exposed 12 consecutive weekdays to 50 parts per billion TDI vapor showed elevated total serum IgE and increased TDI-specific IgG titers. Breathing rates were decreased corresponding with increased inspiratory time. TDI exposure elevated IL-4, IL-5, IL-13, and IFN-γ mRNA expression in the nasal mucosa, suggesting a mixed Th1/Th2 immune response. Expressions of mRNA for proinflammatory cytokines and adhesion molecules were also up-regulated. These cytokine changes corresponded with a marked influx of inflammatory cells into the nasal mucosa, eosinophils being the predominant cell type. Removal from exposure for 2 wk resulted in reduced Ab production, cytokine mRNA expression, and cellular inflammation. Subsequent challenge with 50 parts per billion TDI vapor resulted in robust up-regulation of Ab production, cytokine gene expression, as well as eosinophilic inflammation in the nasal mucosa. There were no associated changes in the lung. The present model shows that TDI inhalation induces immune-mediated allergic rhinitis, displaying the major features observed in human disease. Future studies will use this model to define disease mechanisms and examine the temporal/dose relationship between TDI-induced rhinitis and asthma.

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“…Agonists of TRPV1 and TRPA1, such as capsaicin, acrolein, or chlorine, are potent tussive agents and have been associated with allergic and occupational asthma and reactive airway dysfunction syndrome (RADS) (12,(17)(18)(19)(20)(21)(22)(23). Potential endogenous TRPA1 agonists include reactive oxygen species, hypochlorite, and lipid peroxidation products (18,(24)(25)(26).…”

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.

400

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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Diisocyanate asthma: clinical aspects and immunopathogenesis

Cited by 138 publications

References 76 publications

Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Inhalation of Toluene Diisocyanate Vapor Induces Allergic Rhinitis in Mice

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

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