1. Academic Validation
  2. Protective effects of 4-octyl itaconate against inflammatory response in angiotensin II-induced oxidative stress in human primary retinal pigment epithelium

Protective effects of 4-octyl itaconate against inflammatory response in angiotensin II-induced oxidative stress in human primary retinal pigment epithelium

  • Biochem Biophys Res Commun. 2021 Jun 11;557:77-84. doi: 10.1016/j.bbrc.2021.03.113.
Xinyu Fu 1 Mingxing Wu 1 Xiyuan Zhou 2
Affiliations

Affiliations

  • 1 The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.
  • 2 The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China. Electronic address: zhouxiyuan2002@aliyun.com.
Abstract

4-octyl itaconate (OI) is one kind of cell-permeable derivative of itaconate to regulate inflammation and oxidative stress. However, its effects on the angiotensin II (Ang II)-induced inflammatory response and oxidative stress in human primary retinal pigment epithelium (hRPE) cells as well as its underlying mechanisms were unclear. In this study, we found that OI suppressed changes in pro-inflammatory cytokines (MCP-1, IL-8, and IL-6) and Reactive Oxygen Species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) via activation of Nrf2 signaling in Ang II-treated hRPE cells. A total of 645 differentially expressed long non-coding RNAs (lncRNAs) and 455 mRNAs were identified by microarray analysis. Ten lncRNAs were analyzed using the Coding-non-coding gene co-expression (CNC) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, revealing that many differentially expressed lncRNAs were enriched in immune response-related pathways, such as IL-17, TNF, and NOD-like receptor signaling. This finding suggested that OI inhibits Ang II-induced inflammatory response and oxidative stress by activating Nrf2 signaling in hRPE cells. We also provided a novel perspective on the role of lncRNAs in the protective effects of OI.

Keywords

4-Octyl itaconate; Inflammatory response; Long non-coding RNAs; Oxidative stress; RPE.

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