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Disruption in the balance between apolipoprotein A-I and mast cell chymase in chronic hypersensitivity pneumonitis.

ABSTRACT: BACKGROUND:Apolipoprotein A-I (apoA-I) has an antifibrotic effect in idiopathic pulmonary fibrosis. Although pulmonary fibrosis is associated with poor prognosis of patients with hypersensitivity pneumonitis (HP), little is known regarding the role of apoA-I in the pathogenesis of HP. METHODS:Two-dimensional electrophoresis, immunoblotting, and enzyme-linked immunosorbent assays were performed for the identification and quantification of apoA-I in bronchoalveolar lavage fluid (BALF) from patients with acute and chronic HP. To investigate the degradation of apoA-I, apoA-I was incubated with BALF. Moreover, the role of apoA-I in TGF-?1-induced epithelial-mesenchymal transition of A549 cells was examined. RESULTS:The concentration of apoA-I in the BALF was significantly lower in chronic HP (n?=?56) compared with acute HP (n?=?31). The expression level of apoA-I was also low in the lung tissues of chronic HP. ApoA-I was degraded by BALF from HP patients. The number of chymase-positive mast cells in the alveolar parenchyma was inversely correlated with apoA-I levels in the BALF of chronic HP patients. In vitro experiment using A549 cells, untreated apoA-I inhibited TGF-?1-induced epithelial-mesenchymal transition, although this trend was not observed in the chymase-treated apoA-I. CONCLUSIONS:A decrease of apoA-I was associated with the pathogenesis of chronic HP in terms of pulmonary fibrosis and mast cell chymase attenuated the protective effect of apoA-I against pulmonary fibrosis. Furthermore, apoA-I could be a crucial molecule associated with lung fibrogenesis of HP.

SUBMITTER: Inoue Y

PROVIDER: S-EPMC7654418 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Disruption in the balance between apolipoprotein A-I and mast cell chymase in chronic hypersensitivity pneumonitis.

Inoue Yukihisa Y Okamoto Tsukasa T Honda Takayuki T Nukui Yoshihisa Y Akashi Takumi T Takemura Tamiko T Tozuka Minoru M Miyazaki Yasunari Y

Immunity, inflammation and disease 20201004 4

<h4>Background</h4>Apolipoprotein A-I (apoA-I) has an antifibrotic effect in idiopathic pulmonary fibrosis. Although pulmonary fibrosis is associated with poor prognosis of patients with hypersensitivity pneumonitis (HP), little is known regarding the role of apoA-I in the pathogenesis of HP.<h4>Methods</h4>Two-dimensional electrophoresis, immunoblotting, and enzyme-linked immunosorbent assays were performed for the identification and quantification of apoA-I in bronchoalveolar lavage fluid (BAL ...[more]

PMID: 33016012

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Project description:BackgroundChronic hypersensitivity pneumonitis (CHP) is an immune-mediated interstitial lung disease (ILD) caused by inhalational exposure to environmental antigens, resulting in parenchymal fibrosis. By definition, a diagnosis of CHP assumes a history of antigen exposure, but only half of all patients eventually diagnosed with CHP will have a causative antigen identified. Individual clinician variation in eliciting a history of antigen exposure may affect the frequency and confidence of CHP diagnosis.MethodsA list of potential causative exposures were derived from a systematic review of the literature. A Delphi method was applied to an international panel of ILD experts to obtain consensus regarding technique for the elicitation of exposure to antigens relevant to a diagnosis of CHP. The consensus threshold was set at 80% agreement, and median ≤ 2, interquartile range = 0 on a 5-point Likert scale (1, strongly agree; 2, tend to agree; 3, neither agree nor disagree; 4, disagree; 5, strongly disagree).ResultsIn two rounds, 36/40 experts participated. Experts agreed on 18 exposure items to ask every patient with suspected CHP. Themes included CHP inducing exposures, features that contribute to an exposure's relevance, and quantification of a relevant exposure. Based on the results from the literature review and Delphi process, a CHP exposure assessment instrument was derived. Using cognitive interviews, the instrument was revised by patients with ILD for readability and usability.ConclusionsThis Delphi survey provides items that ILD experts agree are important to ask in all patients presenting with suspected CHP and provides basis for a systematically derived CHP exposure assessment instrument. Clinical utility of this exposure assessment instrument may be affected by different local prevalence patterns of exposures. Ongoing research is required to clinically validate these items and consider their impact in more geographically diverse settings.

Dataset Information

Disruption in the balance between apolipoprotein A-I and mast cell chymase in chronic hypersensitivity pneumonitis.

Publications

Disruption in the balance between apolipoprotein A-I and mast cell chymase in chronic hypersensitivity pneumonitis.

Similar Datasets

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