Transforming growth factor-β1 and eosinophil-derived neurotoxins contribute to the development of work-related respiratory symptoms in bakery workers

Abstract

Background: In baker's asthma previous studies suggest that adaptive and innate immunity are involved in the development of work-related respiratory symptoms (WRS), where we hypothesized that epithelial cells derive airway inflammation through modulating the release of inflammatory cytokines. Thus, we conducted this study to investigate the role of epithelial cell-derived cytokines in the development of WRS among bakery workers. Methods: We recruited 385 wheat-exposed subjects with WRS (WRSþ)/without WRS (WRS-) working in a single industry and 243 unexposed controls from Ajou Medical Center (Suwon, South Korea). Levels of epithelial cell-derived cytokines (interleukin [IL-8], transforming growth factor-b1 [TGF-b1], eotaxin-2) and inflammatory mediators (eosinophil-derived neurotoxins [EDN]) in sera or cell-free supernatants were measured by ELISA. Human airway epithelial cells (HAECs), A549, were stimulated by wheat flour extracts and co-cultured with peripheral blood neutrophils isolated from 4 asthmatic patients. Results: Serum TGF-b1 levels were significantly lower in exposed subjects than in unexposed controls, in the WRSþ group than in the WRS-group (P < 0.001 for each). The WRSþ group had a significantly higher level of serum EDN than the WRS-group (P < 0.001). Serum TGF-b1 and EDN levels predicted the development of WRS in exposed subjects (area under the curve [AUC] ¼ 0.719, 72.4% sensitivity/70% specificity; AUC ¼ 0.759, 78.6% sensitivity/60% specificity). From wheat-stimulated HAECs, TGF-b1 release peaked at 6 hours after wheat exposure, while eotaxin-2 peaked at 12 hours. Co-culture of HAECs with neutrophils did not affect TGF-b1 release. Conclusions: Our results suggest that TGF-b1 may contribute to develop type-2 airway inflammation and WRS. Serum TGF-b1/EDN levels may be potential serum biomarkers for predicting WRS among bakery workers.

Benzo(a)pyrene Enhanced Dermatophagoides Group 1 (Der f 1)-Induced TGFβ1 Signaling Activation Through the Aryl Hydrocarbon Receptor–RhoA Axis in Asthma

“…On one hand, TGFβ1 can modulate lineage differentiation of T cells into different effector T cell subsets (52). On the other hand, TGFβ1 is a cofactor of innate lymphoid cells to induce type-2 airway inflammation and key features of allergic diseases (34,53). Thus, it is pivotal to determine how the increased TGFβ1 production is regulated, which offers novel insights into the mechanisms that lead to allergic airway inflammation.…”