Role of vitamin D-binding protein in isocyanate-induced occupational asthma.
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.
Department of Pharmacology and Chronic Inflammatory, Disease Research Center, Ajou University School of Medicine, Suwon 443-721, Korea.
Sung-Ho
SH
Kim
Gil-Soon
GS
Choi
Young-Hee
YH
Nam
Joo-Hee
JH
Kim
Gyu-Young
GY
Hur
Seung-Hyun
SH
Kim
Sang Myun
SM
Park
Hae-Sim
HS
Park
D000328:Adult; D000818:Animals; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D002460:Cell Line; D004847:Epithelial Cells; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017953:Isocyanates / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity; D014809:Vitamin D-Binding Protein / Q000097:blood*
D017953:Isocyanates; D014809:Vitamin D-Binding Protein; D014051:Toluene 2,4-Diisocyanate