Yonsei Med J.  2018 Dec;59(10):1214-1221. 10.3349/ymj.2018.59.10.1214.

Serum Periostin Levels: A Potential Serologic Marker for Toluene Diisocyanate-Induced Occupational Asthma

• Lee JH
• Kim SH
• Choi Y
• Trinh HK
• Yang EM
• Ban GY
• Shin YS
• Ye YM
• Izuhara K
• Park HS

• KMID: 2426336
• DOI: http://doi.org/10.3349/ymj.2018.59.10.1214

Abstract

PURPOSE
Toluene diisocyanate (TDI) is a leading cause of occupational asthma (OA). Periostin is a matricellular protein implicated in type 2 immunity-driven asthma. Its pathogenic role in TDI-OA has not been completely elucidated. The present study was performed to investigate the role of periostin in TDI-OA.
MATERIALS AND METHODS
Serum periostin levels were measured in subjects with TDI-OA, asymptomatic TDI-exposure controls (AECs), non-occupational asthmatics (NAs), and unexposed normal controls (NCs). To understand the mechanism by which TDI induces periostin production, primary small airway epithelial cells (SAECs) were cultured under stimulation of TDI and neutrophils from asthmatic patients.
RESULTS
Fifty-three subjects with TDI-OA, 71 AECs, 67 NAs, and 83 NCs were enrolled. Serum periostin levels were significantly higher in TDI-OA subjects than in AECs (p=0.001), NAs (p < 0.001), and NCs (p < 0.001). In TDI-exposed subjects (TDI-OA and AEC), the PC20 methacholine levels were significantly lower in subjects with a higher periostin level than in those with a lower periostin level. TDI exposure did not increase periostin production directly by SAECs; however, periostin production increased significantly after co-culture with TDI and neutrophils, which was suppressed by an antioxidant. In addition, increased release of TGF-β1 was noted from SAECs when exposed to TDI and neutrophils, which was also suppressed by an antioxidant.
CONCLUSION
These results suggest that an increased periostin level may contribute to the progression of airway inflammation to remodeling in TDI-exposed workers. A high serum periostin level is a potential serologic marker of the phenotype of TDI-OA.

Keyword

Diisocyanate; occupational asthma; periostin; neutrophils; reactive oxygen species

MeSH Terms

Asthma
Asthma, Occupational*
Coculture Techniques
Epithelial Cells
Humans
Inflammation
Methacholine Chloride
Neutrophils
Phenotype
Reactive Oxygen Species
Toluene 2,4-Diisocyanate
Toluene*
Methacholine Chloride
Reactive Oxygen Species
Toluene
Toluene 2,4-Diisocyanate

Figure

• 

  Fig. 1 Comparison of serum periostin levels in the four study groups (subjects with TDI-OA, AEC, subjects with NA, and NCs). Periostin levels were measured using ELISA. Significantly increased serum periostin levels were noted in TDI-OA, compared to AEC, NA, and NC. TDI, toluene diisocyanate; TDI-OA, TDI-induced occupational asthma; AEC, asymptomatic TDI-exposure control; NA, non-occupational asthma; NC, healthy normal control. Results are presented as means±SEM.

• 

  Fig. 2 TDI-HSA conjugate-induced neutrophil activation according to ROS production. (A) Flow cytometry analysis of ROS production measured by the MFI of fluorescent probe H2DCFDA. (B) There was no significant effect of TDI-HSA conjugate on the production of IL-1β by neutrophils. *p<0.01 obtained by one-way ANOVA with Bonferroni post hoc test. TDI, toluene diisocyanate; PBS, phosphate buffered saline; TDI-HSA, TDI-human serum albumin; NAC, N-Acetyl-L-cysteine; ROS, reactive oxygen species; MFI, mean fluorescence intensity; H2DCFDA, 2′,7′-dichlorodihydrofluorescein diacetate; n.s., not significant.

• 

  Fig. 3 Effects of TDI-HSA conjugate on the induction of immune responses by neutrophils in airway epithelial cells. Concentrations of (A) IL-8, (B) periostin, and (C) TGF-β1 released from airway epithelial cells in the presence of neutrophils under trans-well. Correlation of periostin with (D) IL-8 and TGF-β1, as well as with (E) periostin and (F) IL-8. *p<0.05, †p<0.01, ‡p<0.001 obtained one-way ANOVA with Bonferroni post hoc test. TDI, toluene diisocyanate; TDI-HSA, TDI-human serum albumin; SAEC, small airway epithelial cell; NAC, N-Acetyl-L-cysteine; n.s., not significant; Neu, neutrophils.

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