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  3. Long non-coding RNA lncC11orf54-1 modulates neuroinflammatory responses by activating NF-κB signaling during meningitic Escherichia coli infection

Long non-coding RNA lncC11orf54-1 modulates neuroinflammatory responses by activating NF-κB signaling during meningitic Escherichia coli infection

  • Mol Brain. 2022 Jan 3;15(1):4. doi: 10.1186/s13041-021-00890-8.
Bojie Xu 1 2,  Ruicheng Yang 1 2,  Bo Yang 1 2,  Liang Li 1 2,  Jiaqi Chen 1 2,  Jiyang Fu 1 2,  Xinyi Qu 1 2,  Dong Huo 1 2,  Chen Tan 1 2 3 4,  Huanchun Chen 1 2 3 4,  Zhong Peng 1 2,  Xiangru Wang 5 6 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
  • 2 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China.
  • 3 Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, Hubei, China.
  • 4 International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, Hubei, China.
  • 5 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China. wangxr228@mail.hzau.edu.cn.
  • 6 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China. wangxr228@mail.hzau.edu.cn.
  • 7 Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, Hubei, China. wangxr228@mail.hzau.edu.cn.
  • 8 International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, Hubei, China. wangxr228@mail.hzau.edu.cn.
PMID: 34980188 DOI: 10.1186/s13041-021-00890-8
Abstract

Escherichia coli is the most common gram-negative pathogenic bacterium causing meningitis. It penetrates the blood-brain barrier (BBB) and activates nuclear factor kappa B (NF-κB) signaling, which are vital events leading to the development of meningitis. Long non-coding RNAs (lncRNAs) have been implicated in regulating neuroinflammatory signaling, and our previous study showed that E. coli can induce differential expression of lncRNAs, including lncC11orf54-1, in human brain microvascular endothelial cells (hBMECs). The hBMECs constitute the structural and functional basis for the BBB, however, it is unclear whether lncRNAs are involved in the regulation of inflammatory responses of hBMECs during meningitic E. coli Infection. In this study, we characterized an abundantly expressed lncRNA, lncC11orf54-1, which was degraded by translocated coilin to produce mgU2-19 and mgU2-30 in hBMECs during E. coli Infection. Functionally, lncC11orf54-1-originated non-coding RNA mgU2-30 interacted with interleukin-1 receptor-associated kinase 1 (IRAK1) to induce its oligomerization and autophosphorylation, thus promoting the activation of NF-κB signaling and facilitating the production of pro-inflammatory cytokines. In summary, our study uncovers the involvement of lncC11orf54-1 in IRAK1-NF-κB signaling, and it functions as a positive regulator of inflammatory responses in meningitic E. coli-induced neuroinflammation, which may be a valuable therapeutic and diagnostic target for Bacterial meningitis.

Keywords

Blood–brain barrier; Brain microvascular endothelial cells; LncC11orf54-1; Meningitic Escherichia coli; NF-κB signaling; Neuroinflammation.

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