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

Molecular Brain

Bojie Xu¹  Dong Huo¹  Liang Li¹  Xinyi Qu¹  Bo Yang¹  Zhong Peng¹  Jiyang Fu¹  Ruicheng Yang¹  Jiaqi Chen¹  Xiangru Wang²  Chen Tan²  Huanchun Chen² 

[1] State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China;Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China;State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China;Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China;Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People’s Republic of China, Wuhan, Hubei, China;International Research Center for Animal Disease, Ministry of Science and Technology of the People’s Republic of China, Wuhan, Hubei, China;

关键词: LncC11orf54-1;    Neuroinflammation;    Brain microvascular endothelial cells;    NF-κB signaling;    Escherichia coli;    Blood–brain barrier;   

DOI  :  10.1186/s13041-021-00890-8

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY