ArticleChemical research in toxicology2015
Glutathione reaction products with a chemical allergen, methylene-diphenyl diisocyanate, stimulate alternative macrophage activation and eosinophilic airway inflammation.
Article in Chemical research in toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Circular RNA hsa_circ_0099188 regulates inducible nitric oxide synthase and chemokine transcription in macrophages by targeting the hsa-miR-381-3p/PPP3CA and hsa-miR-381-3p/KLF4 pathways in response to 4,4'-methylene diphenyl diisocyanate-glutathione conjugate exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Circular RNACells · 2024Article
- Human keratinocyte response to 4,4'-methylene diphenyl diisocyanate-glutathione conjugate exposure.Xenobiotica; the fate of foreign compounds in biological systems · 2024Article
- MicroRNA-mediated Krüppel-like factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4'-methylene diphenyl diisocyanate exposed macrophages.Xenobiotica; the fate of foreign compounds in biological systems · 2024Article
- Lung Gene Expression Suggests Roles for Interferon-Stimulated Genes and Adenosine Deaminase Acting against RNA-1 in Pathologic Responses to Diisocyanate.Chemical research in toxicology · 2024Article
- 4,4'-Methylene diphenyl diisocyanate exposure induces expression of alternatively activated macrophage-associated markers and chemokines partially through Krüppel-like factor 4 mediated signaling in macrophages.Xenobiotica; the fate of foreign compounds in biological systems · 2023Article
- Total Reactive Isocyanate Group (TRIG) Measurement: A Commentary.Annals of work exposures and health · 2023Article
- Glutathione reactivity with aliphatic polyisocyanates.PloS one · 2022Article
- MicroRNA-mediated calcineurin signaling activation induces CCL2, CCL3, CCL5, IL8, and chemotactic activities in 4,4'-methylene diphenyl diisocyanate exposed macrophages.Xenobiotica; the fate of foreign compounds in biological systems · 2021Article
- Analysis of Lung Gene Expression Reveals a Role for ClAmerican journal of respiratory cell and molecular biology · 2020Article
- Acute 4,4'-Methylene Diphenyl Diisocyanate Exposure-Mediated Downregulation of miR-206-3p and miR-381-3p Activates Inducible Nitric Oxide Synthase Transcription by Targeting Calcineurin/NFAT Signaling in Macrophages.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Dilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure?Chemical research in toxicology · 2019Article
- LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.EC pharmacology and toxicology · 2019Article
- Mass spectrometry-based analysis of murine bronchoalveolar lavage fluid following respiratory exposure to 4,4'-methylene diphenyl diisocyanate aerosol.Xenobiotica; the fate of foreign compounds in biological systems · 2018Article
- Reaction products of hexamethylene diisocyanate vapors with "self" molecules in the airways of rabbits exposed via tracheostomy.Xenobiotica; the fate of foreign compounds in biological systems · 2018Article
- Identification of novel reaction products of methylene-bis-phenylisocyanate ("MDI") with oxidized glutathione in aqueous solution and also during incubation of MDI with a murine hepatic S9 fraction.Toxicology in vitro : an international journal published in association with BIBRA · 2016Article
- Immunochemical detection of the occupational allergen, methylene diphenyl diisocyanate (MDI), in situ.Journal of immunological methods · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH-MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position (414)K, a preferred site of MDI reactivity on human albumin. The (414)K-MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric (S,N'-linked) bis(GSH)-MDI conjugates. Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses.
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