Endocrine-disrupting chemical exposure augments neutrophilic inflammation in severe asthma through the autophagy pathway. (May 2023)

• Record Type: Journal Article
• Authors: Quoc, Quang Luu; Cao, Thi Bich Tra; Kim, Seo-Hee; Choi, Yeji; Ryu, Min Sook; Choi, Youngwoo; Park, Hae-Sim; Shin, Yoo Seob
• Is Part Of: Food and chemical toxicology. Volume 175(2023)
• Publication Date: 2023-05
• Subjects: Asthma -- Endocrine disrupting chemicals -- Macrophages -- Neutrophil extracellular traps -- Neutrophilic inflammation; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2023.113699
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Corticosteroid resistance, progressive lung function decline, and frequent asthma exacerbations are the hallmarks of neutrophilic asthma (NA). However, the potential contributors and their mechanisms of NA aggravation have not yet been fully clarified. This study was conducted to assess the precise mechanism and inflammatory effects of endocrine-disrupting chemicals using mono-n-butyl phthalate (MnBP) on an NA model. BALB/c mice from normal control and LPS/OVA-induced NA groups were treated with or without MnBP. The effects of MnBP on the airway epithelial cells (AECs), macrophages (Mφ), and neutrophils were investigated in vitro and in vivo . NA mice exposed to MnBP had significantly increased airway hyperresponsiveness, total and neutrophil cell counts in the bronchoalveolar lavage fluid, and the percentage of M1Mφ in the lung tissues compared to those non-exposed to MnBP. In in vitro study, MnBP induced the human neutrophil activation to release neutrophil DNA extracellular traps, Mφ polarizing toward M1Mφ, and AEC damage. Treatment with hydroxychloroquine (an autophagy inhibitor) reduced the effects of MnBP in vivo and in vitro . The results of our study suggest that MnBP exposure may increase the risk of neutrophilic inflammation in severe asthma and autophagy pathway-targeted therapeutics can help control MnBP-induced harmful effects in asthma. Graphical abstract: Suggested pathophysiological pathways of MnBP . Figures were drawn by using pictures from Servier Medical Art (https://smart.servier.com/ ), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/ ). AECs, airway epithelial cells; BALF, bronchoalveolar lavage fluid; dsDNA, double-stranded DNA; HCQ, hydroxychloroquine; LPS, lipopolysaccharides; Mφ, macrophages; MnBP, mono-n-butyl phthalate; MPO, myeloperoxidase; NE, neutrophil elastase; OVA, ovalbumin; TNF-α, tumour necrosis factor α. Image 1 Highlights: The exposure to MnBP enhances neutrophilic inflammation in asthma in vivo . Administration of MnBP activates autophagy-related proteins in lung tissue in vivo . MnBP induces the disruptions of tight junctions and macrophage activation in vitro . MnBP activates autophagy pathway inducing neutrophil activation in vitro . Autophagy inhibitor (HCQ) may inhibit the harmful effects of MnBP.