The development of a serological marker for early diagnosis of
isocyanate-induced
occupational asthma (
isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of
vitamin D-binding protein (VDBP) was upregulated in the patients with
isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for
isocyanate-OA among exposed workers and its role in the pathogenesis of
isocyanate-OA. Three study groups including 61 patients with
isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of
isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (≥311 μg/ml) had significantly lower PC(20)
methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of
megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore,
toluene diisocyanate (TDI) increased
VEGF production and secretion from this epithelial cells by suppression of
1,25-dihydroxycholecalciferol [
1,25(OH)(2)D(3)] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of
isocyanate-OA among workers exposed to
isocyanate. The TDI-induced
VEGF production/ secretion was reversed by
1,25(OH)(2)D(3) treatment, which may provide a potential therapeutic strategy for patients with
isocyanate-OA.