Biomarkers Predicting Isocyanate-Induced Asthma

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 microg/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.

The Effect of Substance P on Osteoclastogenesis and Osteoclastic Bone Resorption in vitro / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Osteoclasts are the principal cell of bone resorption playing a major role in focal bone erosion associated with cholesteatoma. This study was conducted in order to investigate direct effect of substance P (SP) on osteoclastogenesis and osteoclastic bone resorption in vitro. MATERIALS AND METHOD: SP dose response was measured in receptor activator for NF-kappaB ligand (RANKL)-induced mouse osteoclast culture and osteoclastic bone resorption assay. RT-PCR was performed for the expression of neurokinin(NK) receptor mRNAs in osteoclasts. RESULTS: Treatment with SP (100 nM and 1000 nM) significantly increased osteoclastogenesis. SP (0.1 nM and 1 nM) significantly increased resorption surface area on dentin slices by osteoclasts. Cultured osteoclasts expressed NK-2 receptor mRNA. CONCLUSION: SP has a direct upregulatory effect on osteoclastogenesis and osteoclastic bone resorption that is mediated possibly by NK-2 receptor.