Relationship between neurokinin 2 receptor gene polymorphisms and serum vascular endothelial growth factor levels in patients with toluene diisocyanate‐induced asthma

Ye, Y.-M.; Kang, Young Mi; Kim, S.-H.; Kim, C.-W.; Kim, Hye-Ryoung; Hong, Chae-Seon; Park, C.-S.; Kim, H.-M.; Nahm, Dong Ho; Park, H.-S.

doi:10.1111/j.1365-2222.2006.02547.x

Cited by 15 publications

(15 citation statements)

References 40 publications

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“…63 A role for neurogenic inflammation in isocyanate asthma has been suggested by a Korean study. 64 The authors investigated whether neurokinin 2 receptor (NK2R) gene polymorphisms are associated with the clinical phenotype of TDI asthma. No significant differences in allele, genotype, or haplotype frequencies of the NK2R polymorphisms were present among the groups of subjects with asthma, asymptomatic exposed subjects, and healthy controls.…”

Section: Genetic Aspectsmentioning

confidence: 99%

Mechanisms of occupational asthma

Maestrelli

Boschetto

Fabbri

et al. 2009

Journal of Allergy and Clinical Immunology

189

148

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Section: Genetic Aspectsmentioning

confidence: 99%

Mechanisms of occupational asthma

Maestrelli

Boschetto

Fabbri

et al. 2009

Journal of Allergy and Clinical Immunology

189

148

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“…No significant difference in allele, genotype, or haplotype frequencies of these two SNPs was seen, but subjects with the NK2R 7853GG genotype had higher serum vascular endothelial growth factor (VEGF) levels than those with GA or AA among the TDI-exposed workers, suggesting that the NK2R 7853GG genotype contributes to increased serum VEGF levels, resulting in airway inflammation after TDI exposure, which may be mediated by neurogenic ROS 26. These results suggest that the NK2R 7853G>A polymorphism is a candidate biomarker for TDI OA.…”

Section: Genetic Markersmentioning

confidence: 99%

Biomarkers Predicting Isocyanate-Induced Asthma

Palikhe

Kim

Park

2011

Allergy Asthma Immunol Res

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Three diisocyanates can cause occupational asthma (OA): toluene diisocyanate (TDI), 4,4 diphenylmethane diisocyanate (MDI), and 1,6-hexamethylene diisocyanate (HDI). We analyzed potential biomarkers of isocyanate-induced OA, based on investigated immunologic, genetic, neurogenic, and protein markers, because there is no serological testing method. The prevalence of serum IgG to cytokeratin (CK)18 and CK19 in TDI-OA was significantly higher than in controls, although the prevalence of these antibodies was too low for them to be used as biomarkers. Another candidate biomarker was serum IgG to tissue transglutaminase (tTG), because the prevalence of serum specific IgG to tTG was significantly higher in patients with TDI-OA than in controls. The human leukocyte antigen (HLA) DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be used as a genetic marker for TDI-OA in Koreans via enhanced specific IgE sensitization in exposed subjects. The genetic polymorphisms of catenin alpha 3, alpha-T catenin (CTNNA3) were significantly associated with TDI-OA. Additionally, examining the neurokinin 2 receptor (NK2R) 7853G>A and 11424 G>A polymorphisms, the NK2R 7853GG genotype had higher serum vascular endothelial growth factor (VEGF) levels than the GA or AA genotypes among Korean workers exposed to TDI. To identify new serologic markers using a proteomic approach, differentially expressed proteins between subjects with MDI-OA and asymptomatic exposed controls in a Korean population showed that the optimal serum cutoff levels were 69.8 ng/mL for ferritin and 2.5 µg/mL for transferrin. When these two parameters were combined, the sensitivity was 71.4% and the specificity was 85.7%. The serum cytokine matrix metalloproteinase-9 (MMP-9) level is a useful biomarker for identifying cases of TDI-OA among exposed workers. Despite these possible biomarkers, more effort should be focused on developing early diagnostic biomarkers using a comprehensive approach based on the pathogenic mechanisms of isocyanate-induced OA.

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“…6 In addition, a genome-wide association study of TDI-exposed workers revealed that alpha T-catenin single-nucleotide polymorphisms (SNPs) were significantly associated with the phenotype of TDI-induced OA. Moreover, two SNPs of TRPM8 (rs10803666 and rs12434022, which have been mapped to the TRPM8 gene and are located on 2q37 and 14q31) showed significant associations using a recessive analysis model.…”

Section: Introductionmentioning

confidence: 99%

Toluene diisocyanate exposure induces airway inflammation of bronchial epithelial cells via the activation of transient receptor potential melastatin 8

Kim

Jang

et al. 2017

Exp Mol Med

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Toluene diisocyanate (TDI) is the most important cause of occupational asthma (OA), and various pathogenic mechanisms have been suggested. Of these mechanisms, neurogenic inflammation is an important inducer of airway inflammation. Transient receptor potential melastatin 8 (TRPM8) is a well-established cold-sensing cation channel that is expressed in both neuronal cells and bronchial epithelial cells. A recent genome-wide association study of TDI-exposed workers found a significant association between the phenotype of TDI-induced OA and the single-nucleotide polymorphism rs10803666, which has been mapped to the TRPM8 gene. We hypothesized that TRPM8 located in airway epithelial cells may be involved in the pathogenic mechanisms of TDI-induced OA and investigated its role. Bronchial epithelial cells were treated with TDI in a dose- and time-dependent manner. The expression levels of TRPM8 mRNA and protein were determined by quantitative real-time polymerase chain reaction and western blotting. TDI-induced morphological changes in the cells were evaluated by immunocytochemistry. Alterations in the transcripts of inflammatory cytokines were examined in accordance with TRPM8 activation by TDI. TRPM8 expression at both the mRNA and protein levels was enhanced by TDI in airway epithelial cells. TRPM8 activation by TDI led to significant increases in the mRNA of interleukin (IL)-4, IL-13, IL-25 and IL-33. The increased expression of the cytokine genes by TDI was partly attenuated after treatment with a TRPM8 antagonist. TDI exposure induces increased expression of TRPM8 mRNA in airway epithelial cells coupled with enhanced expression of inflammatory cytokines, suggesting a novel role of TRPM8 in the pathogenesis of TDI-induced OA.

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Relationship between neurokinin 2 receptor gene polymorphisms and serum vascular endothelial growth factor levels in patients with toluene diisocyanate‐induced asthma

Cited by 15 publications

References 40 publications

Mechanisms of occupational asthma

Mechanisms of occupational asthma

Biomarkers Predicting Isocyanate-Induced Asthma

Toluene diisocyanate exposure induces airway inflammation of bronchial epithelial cells via the activation of transient receptor potential melastatin 8

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