Prevention of IL-1 signaling attenuates airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate–induced asthma

Johnson, Victor J.; Yücesoy, Berran; Luster, Michael I.

doi:10.1016/j.jaci.2005.07.008

Cited by 84 publications

(54 citation statements)

References 28 publications

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“…This high reactivity suggests that TDI vapor will rapidly complex with epithelial and mucus proteins, effectively scrubbing it from the incoming air stream and reducing the concentration before reaching the olfactory epithelium in the posterior nasal cavity or the lung. Inhalation exposure paradigms at higher TDI concentrations or longer exposure durations induced lung pathology (10,21,24). This suggests that regional dose is most likely responsible for the pattern of response that will result from TDI vapor exposure, although it is still possible that selective sensitivity of transitional and respiratory epithelial cells vs olfactory epithelial cells plays a role.…”

Section: Discussionmentioning

confidence: 99%

“…Respiratory function was assessed immediately following the final TDI sensitization exposure using unrestrained whole body plethysmography (Buxco Electronics), as previously described (20,24). Mice were placed into individual plethysmographs and allowed to acclimate for 10 min.…”

Section: Assessment Of Airway Functionmentioning

confidence: 99%

“…TDI-specific IgG serum Abs were detected using an ELISA procedure, as previously described (20,24), with modifications where noted. The TDImouse serum albumin conjugate used as the capture Ag was prepared by adding 0.5 ml of dilute TDI (1% in acetone) to 10 ml of mouse serum albumin (5 mg/ml in PBS) using a KDS100 syringe pump (KD Scientific) at 25 l/min.…”

Section: Tdi-specific Igg and Total Serum Ige Detectionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Assessment Of Airway Functionmentioning

confidence: 99%

Section: Tdi-specific Igg and Total Serum Ige Detectionmentioning

confidence: 99%

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Inhalation of Toluene Diisocyanate Vapor Induces Allergic Rhinitis in Mice

Johnson

Yücesoy

Reynolds

et al. 2007

The Journal of Immunology

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“…In vivo and in vitro assays have demonstrated that IL-1␤ can alter airway function by inducing cellular infiltrate, mucus hyperplasia, airway wall thickening, fibrosis, and enlargement of distal air spaces (21,25). Effector mechanisms include secretion of IL-8 (CXCL-8), which has been demonstrated to modulate HASMC contraction and migration mediating airway responsiveness and remodeling in asthmatic patients (9,14,47).…”

mentioning

confidence: 99%

IL-17 enhances IL-1β-mediated CXCL-8 release from human airway smooth muscle cells

Dragon

Rahman²,

Yang³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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December 22, 2006; doi:10.1152/ajplung.00306.2006.-Recent studies into the pathogenesis of airway disorders such as asthma have revealed a dynamic role for airway smooth muscle cells in the perpetuation of airway inflammation via secretion of cytokines and chemokines. In this study, we evaluated whether IL-17 could enhance IL-1␤-mediated CXCL-8 release from human airway smooth muscle cells (HASMC) and investigated the upstream and downstream signaling events regulating the induction of CXCL-8. CXCL-8 mRNA and protein induction were assessed by real-time RT-PCR and ELISA from primary HASMC cultures. HASMC transfected with site-mutated activator protein (AP)-1/NF-B CXCL-8 promoter constructs were treated with selective p38, MEK1/2, and phosphatidylinositol 3-kinase (PI3K) inhibitors to determine the importance of MAPK and PI3K signaling pathways as well as AP-1 and NF-B promoter binding sites. We demonstrate IL-17 induced and synergized with IL-1␤ to upregulate CXCL-8 mRNA and protein levels. Erk1/2 and p38 modulated IL-17 and IL-1␤ CXCL-8 promoter activity; however, IL-1␤ also activated the PI3K pathway. The synergistic response mediating CXCL-8 promoter activity was dependent on both MAPK and PI3K signal transduction pathways and required the cooperation of AP-1 and NF-B cis-acting elements upstream of the CXCL-8 gene. Collectively, our observations indicate MAPK and PI3K pathways regulate the synergy of IL-17 and IL-1␤ to enhance CXCL-8 promoter activity, mRNA induction, and protein synthesis in HASMC via the cooperative activation of AP-1 and NF-B trans-acting elements.

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“…Recent studies have indicated that pro-inflammatory cytokines may be essential inflammatory mediators in the development of asthma. [30][31][32] Pro-inflammatory cytokines are important for the development of airway inflammation by the innate immune system before activation of the adaptive immune system. They also serve as chemoattractants for neutrophils and eosinophils, increasing the AHR.…”

Section: Salmeterol Attenuates Inflammatory Response In Asthma Zl Hu mentioning

confidence: 99%

Salmeterol attenuates the inflammatory response in asthma and decreases the pro-inflammatory cytokine secretion of dendritic cells

Chen

Cai

et al. 2012

Cell Mol Immunol

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Salmeterol is a long-acting b2-agonist that activates adenylate cyclase, causing long-lasting bronchodilation and has been used for many years to control asthma. However, little information is available about the immunoregulatory effects of salmeterol. We found that salmeterol decreases the production of pro-inflammatory cytokines in a model of allergen-challenged mice that expressed tumor-necrosis factor-alpha, interleukin-1 and interleukin-6. Dendritic cells (DCs) are antigen-presenting cells and act as sentinels in the airway. We found that salmeterol (10 25 mol/l) reduced the inflammation caused by lipopolysaccharide (0.1 mg/ml) in activated murine bone marrow-derived DCs. Moreover, western blots demonstrated that this protective effect was mediated partially by inhibiting signaling through the nuclear factor-kappa B (NF-kB), mitogen-activated protein kinase (MAPK) pathways and dramatically decreased levels of p-ERK. We suggest that salmeterol regulates the inflammation of allergen-induced asthma by modulating DCs. In conclusion, we provide evidence that DCs are the target immune cells responsible for the action of salmeterol against asthma.

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Prevention of IL-1 signaling attenuates airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate–induced asthma

Cited by 84 publications

References 28 publications

Inhalation of Toluene Diisocyanate Vapor Induces Allergic Rhinitis in Mice

Inhalation of Toluene Diisocyanate Vapor Induces Allergic Rhinitis in Mice

IL-17 enhances IL-1β-mediated CXCL-8 release from human airway smooth muscle cells

Salmeterol attenuates the inflammatory response in asthma and decreases the pro-inflammatory cytokine secretion of dendritic cells

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