- Title
- 4-Octyl Itaconate Alleviates Airway Eosinophilic Inflammation by Suppressing Chemokines and Eosinophil Development
- Creator
- Yin, Maureen; Wadhwa, Ridhima; Marshall, Jacqueline E.; Gillis, Caitlin M.; Kim, Richard Y.; Dua, Kamal; Palsson-McDermott, Eva M.; Fallon, Padraic G.; Hansbro, Philip M.; O'Neill, Luke A. J.
- Relation
- Journal of Immunology Vol. 212, Issue 1, p. 13-23
- Publisher Link
- http://dx.doi.org/10.4049/jimmunol.2300155
- Publisher
- American Association of Immunologist
- Resource Type
- journal article
- Date
- 2024
- Description
- 4-Octyl itaconate (4-OI) is a derivative of the Krebs cycle-derived metabolite itaconate and displays an array of antimicrobial and anti-inflammatory properties through modifying cysteine residues within protein targets. We have found that 4-OI significantly reduces the production of eosinophil-targeted chemokines in a variety of cell types, including M1 and M2 macrophages, Th2 cells, and A549 respiratory epithelial cells. Notably, the suppression of these chemokines in M1 macrophages was found to be NRF2-dependent. In addition, 4-OI can interfere with IL-5 signaling and directly affect eosinophil differentiation. In a model of eosinophilic airway inflammation in BALB/c mice, 4-OI alleviated airway resistance and reduced eosinophil recruitment to the lungs. Our findings suggest that itaconate derivatives could be promising therapeutic agents for the treatment of eosinophilic asthma.
- Subject
- 4-Octyl itaconate (4-OI); cysteine residues; protein targets; cell types
- Identifier
- http://hdl.handle.net/1959.13/1494747
- Identifier
- uon:53870
- Identifier
- ISSN:0022-1767
- Language
- eng
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