The involvement of copper, circular RNAs, and inflammatory cytokines in chronic respiratory disease. (September 2022)

• Record Type: Journal Article
• Authors: Chen, Zehao; Zhu, Jialu; Zhou, Hanyu; Jia, Yangyang; Ruan, Honglian; Diao, Qinqin; Li, Meizhen; Zheng, Liting; Yao, Shuwei; Guo, Yaozheng; Zhou, Yun; Jiang, Yiguo
• Is Part Of: Chemosphere. Volume 303:Part 2(2022)
• Publication Date: 2022-09
• Subjects: Chronic respiratory disease -- Copper -- circRNA -- Inflammatory cytokines; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2022.135005
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Exposure to high concentrations of copper is associated with pulmonary inflammation and chronic respiratory disease (CRD). Epigenetic modulation of noncoding RNAs contributes to the development of several CRDs. It is unknown whether epigenetic modulation is involved in copper mediated pulmonary inflammation and CRD. We conducted a case-control study of 101 CRD cases and 161 control subjects in Shijiazhuang, China, and evaluated circRNAs and cytokine levels (IL-6 and IL-8) by qPCR and ELISA. Urinary copper concentration was determined by inductively coupled plasma mass spectrometry. Linear mixed models and generalized linear mixed models were used to assess the associations of circRNAs with CRD, urinary copper, and cytokines. We exposed the human bronchial epithelial cell line, 16HBE, to copper and assessed the functional role of a circRNA, circ_0008882, by RNA overexpression. Cellular location of circ_0008882 was assessed by separation of nuclear and cytoplasmic RNAs. Nine circRNAs were associated with an increased risk for CRDs, while the relative expression of circ_0008882 was decreased after copper exposure in vitro and in vivo . Copper exposure stimulated 16HBE cells to release proinflammatory IL-6 and IL-8. The release of the cytokines was inhibited by overexpression of circ_0008882. These results suggest a role for circ_0008882 in the regulation of CRD associated inflammation following copper exposure. Graphical abstract: Image 1 Highlights: Circular RNA, circ_0008882, is related to chronic respiratory disease. Expression of circ_0008882 decreases after copper exposure in vitro and in vivo. IL-6 and IL-8, induced by copper, are inhibited by overexpression of circ_0008882.