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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


TRPM8-mediated alteration in (a) IL-25 and (b) IL-33 transcription in BEAS-2B cells. Each bar represents the mean values normalized to untreated controls for the cell populations and standard deviations. Values significantly different from untreated and TDI (1 mM)-treated cells are indicated by * and #, respectively (paired t-test, *, #, P<0.05; **, ##, P<0.01; ***, ###, P<0.001). TDI, toluene diisocyanate.
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fig7: TRPM8-mediated alteration in (a) IL-25 and (b) IL-33 transcription in BEAS-2B cells. Each bar represents the mean values normalized to untreated controls for the cell populations and standard deviations. Values significantly different from untreated and TDI (1 mM)-treated cells are indicated by * and #, respectively (paired t-test, *, #, P<0.05; **, ##, P<0.01; ***, ###, P<0.001). TDI, toluene diisocyanate.

Mentions: The coupling of TRPM8 activation in BEAS-2B cells with enhanced expression of proinflammatory cytokines (IL-6 and IL-8), epithelial-driven cytokines (IL-25 and IL-33) and Th2 cytokines (IL-4 and IL-13) was evaluated following treatment with TDI. No alteration was observed in IL-6 and IL-8 transcripts after TDI exposure. Instead, co-treatment with TDI and BCTC resulted in significantly lower IL-6 and IL-8 transcripts compared with the control (Figure 5). The degree of decrement in IL-6 by BCTC was similar to that by dexamethasone. The TRPM8 activation by TDI led to a significant increase in the transcripts for IL-4, IL-13 and IL-25 (Figures 6 and 7). The transcript for IL-33 tended to increase with 1 mM of TDI, but this change did not reach statistical significance. TDI-induced increases in cytokines gene expression were partly attenuated after co-treatment with BCTC and dexamethasone (Figures 6 and 7).


Toluene diisocyanate exposure induces airway inflammation of bronchial epithelial cells via the activation of transient receptor potential melastatin 8
TRPM8-mediated alteration in (a) IL-25 and (b) IL-33 transcription in BEAS-2B cells. Each bar represents the mean values normalized to untreated controls for the cell populations and standard deviations. Values significantly different from untreated and TDI (1 mM)-treated cells are indicated by * and #, respectively (paired t-test, *, #, P<0.05; **, ##, P<0.01; ***, ###, P<0.001). TDI, toluene diisocyanate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382555&req=5

fig7: TRPM8-mediated alteration in (a) IL-25 and (b) IL-33 transcription in BEAS-2B cells. Each bar represents the mean values normalized to untreated controls for the cell populations and standard deviations. Values significantly different from untreated and TDI (1 mM)-treated cells are indicated by * and #, respectively (paired t-test, *, #, P<0.05; **, ##, P<0.01; ***, ###, P<0.001). TDI, toluene diisocyanate.
Mentions: The coupling of TRPM8 activation in BEAS-2B cells with enhanced expression of proinflammatory cytokines (IL-6 and IL-8), epithelial-driven cytokines (IL-25 and IL-33) and Th2 cytokines (IL-4 and IL-13) was evaluated following treatment with TDI. No alteration was observed in IL-6 and IL-8 transcripts after TDI exposure. Instead, co-treatment with TDI and BCTC resulted in significantly lower IL-6 and IL-8 transcripts compared with the control (Figure 5). The degree of decrement in IL-6 by BCTC was similar to that by dexamethasone. The TRPM8 activation by TDI led to a significant increase in the transcripts for IL-4, IL-13 and IL-25 (Figures 6 and 7). The transcript for IL-33 tended to increase with 1 mM of TDI, but this change did not reach statistical significance. TDI-induced increases in cytokines gene expression were partly attenuated after co-treatment with BCTC and dexamethasone (Figures 6 and 7).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.