Meningitic Escherichia coli-induced upregulation of PDGF-B and ICAM-1 aggravates blood-brain barrier disruption and neuroinflammatory response

Journal of Neuroinflammation

Kwang Sik Kim¹  Liang Li²  Rui-Cheng Yang²  Xin-Yi Qu²  Ji-Yang Fu²  Si-Yu Xiao²  Bo-Jie Xu²  Yu-Jin Lv³  Xiang-Ru Wang⁴  Nouman Amjad⁴  Chen Tan⁴  Huan-Chun Chen⁴ 

[1] 0000 0001 2171 9311, grid.21107.35, Department of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 21287, Baltimore, MD, USA;0000 0004 1790 4137, grid.35155.37, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, 430070, Wuhan, Hubei, China;0000 0004 1790 4137, grid.35155.37, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, 430070, Wuhan, Hubei, China;0000 0000 9139 560X, grid.256922.8, College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, 450046, Zhengzhou, Henan, China;0000 0004 1790 4137, grid.35155.37, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, 430070, Wuhan, Hubei, China;0000 0004 1790 4137, grid.35155.37, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, 430070, Wuhan, Hubei, China;

关键词: Blood-brain barrier;    PDGF-B;    ICAM-1;    Permeability;    Neuroinflammation;   

DOI  :  10.1186/s12974-019-1497-1

来源: publisher

【 摘 要 】

BackgroundBlood-brain barrier (BBB) disruption and neuroinflammation are considered key mechanisms of pathogenic Escherichia coli invasion of the brain. However, the specific molecules involved in meningitic E. coli-induced BBB breakdown and neuroinflammatory response remain unclear. Our previous RNA-sequencing data from human brain microvascular endothelial cells (hBMECs) revealed two important host factors: platelet-derived growth factor-B (PDGF-B) and intercellular adhesion molecule-1 (ICAM-1), which were significantly upregulated in hBMECs after meningitic E. coli infection. Whether and how PDGF-B and ICAM-1 contribute to the development of E. coli meningitis are still unclear.MethodsThe western blot, real-time PCR, enzyme-linked immunosorbent assay, immunohistochemistry, and immunofluorescence were applied to verify the significant induction of PDGF-B and ICAM-1 by meningitic E. coli in vivo and in vitro. Evan’s blue assay and electric cell-substrate impedance sensing assay were combined to identify the effects of PDGF-B on BBB permeability. The CRISPR/Cas9 technology, cell-cell adhesion assay, and electrochemiluminescence assay were used to investigate the role of ICAM-1 in neuroinflammation subversion.ResultsWe verified the significant induction of PDGF-B and ICAM-1 by meningitic E. coli in mouse as well as monolayer hBMECs models. Functionally, we showed that the increase of PDGF-B may directly enhance the BBB permeability by decreasing the expression of tight junction proteins, and the upregulation of ICAM-1 contributed to neutrophils or monocytes recruitment as well as neuroinflammation subversion in response to meningitic E. coli infection.ConclusionsOur findings demonstrated the roles of PDGF-B and ICAM-1 in mediating bacterial-induced BBB damage as well as neuroinflammation, providing new concepts and potential targets for future prevention and treatment of bacterial meningitis.

【 授权许可】

CC BY