Oxidative stress stimulation leads to cell-specific oxidant and antioxidant responses in airway resident and inflammatory cells

• Published in: Life sciences (1973) 2023-02, Vol.315, p.121358-121358, Article 121358
• Main Authors: Akel Bilgic, Hayriye, Kilic, Busra, Kockaya, Berfin Doga, Sarac, Basak Ezgi, Kilic Suloglu, Aysun, Kalayci, Omer, Karaaslan, Cagatay
• Format: Article
• Language: English
• Subjects: Antioxidants - metabolism; Cell Line; Endothelial cells; Eosinophils, neutrophils and monocytes; Epithelial cells; Fibroblast; Gene expression; Humans; Oxidants - metabolism; Oxidative Stress - physiology; Oxidative stress and antioxidant response; Reactive Oxygen Species - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.121358

The imbalance between reactive oxygen species (ROS) and the antioxidant response has been linked to various airway diseases, including asthma. However, knowledge on cell-specific responses of the airway resident and inflammatory cells against increased oxidant stress is very limited. We aim to better understand the cell-specific antioxidant response that contributes to the pathophysiology of lung disease in response to oxidative stress. The human cell lines of epithelial, fibroblast, endothelial, monocyte, eosinophil and neutrophil were incubated with tert-butyl hydroperoxide (tBHP) or cigarette smoke condensate (CSC). Following stimulation, cell viability, total oxidant and antioxidant activity were assessed in both residential and inflammatory cells. Human Oxidative Stress Plus RT2 Profiler PCR array was used to determine 84 gene expression differences in oxidant and antioxidant pathways following oxidant stimulus in all cells. We showed that various cell types respond differently to oxidative stress inducers, with distinct gene expression and oxidant-antioxidant generation. Most importantly, eosinophils increased the activity of all main antioxidant enzymes in response to both oxidants. Monocytes, on the other hand, showed no change in response to each stimulation, whereas neutrophils only increased their CAT activity in response to both stimuli. The increase in NRF2-regulated genes HSPA1A, HMOX1 and DUSP1 after both tBHP and CSC in epithelial cells and fibroblasts indicates Nfr2 pathway activation. This study advances our knowledge of the molecular and cellular mechanisms of cell-specific antioxidant response upon exposure to oxidative stress. Additionally, our observations imply that the eosinophils' distinct biological response may be utilized for endotype-based cell-targeted antioxidant therapy. [Display omitted] •The antioxidant response of lung-resident and inflammatory cells differs by cell type and source of oxidative stress.•Eosinophils respond uniquely to tBHP and CSC with increased activity of antioxidants, which may help treat T2-type asthma.•This study provides potential support for cell-based antioxidant therapy, noting that each cell has a unique redox response.