TGF1-induced hedgehog signaling suppresses the immune response of brain microvascular endothelial cells elicited by meningitic Escherichia coli
CELL COMMUNICATION AND SIGNALING(2024)
摘要
Background Meningitic Escherichia coli (E. coli) is the major etiological agent of bacterial meningitis, a life-threatening infectious disease with severe neurological sequelae and high mortality. The major cause of central nervous system (CNS) damage and sequelae is the bacterial-induced inflammatory storm, where the immune response of the blood-brain barrier (BBB) is crucial. Methods Western blot, real-time PCR, enzyme-linked immunosorbent assay, immunofluorescence, and dual-luciferase reporter assay were used to investigate the suppressor role of transforming growth factor beta 1 (TGF beta 1) in the immune response of brain microvascular endothelial cells elicited by meningitic E. coli. Result In this work, we showed that exogenous TGF beta 1 and induced noncanonical Hedgehog (HH) signaling suppressed the endothelial immune response to meningitic E. coli infection via upregulation of intracellular miR-155. Consequently, the increased miR-155 suppressed ERK1/2 activation by negatively regulating KRAS, thereby decreasing IL-6, MIP-2, and E-selectin expression. In addition, the exogenous HH signaling agonist SAG demonstrated promising protection against meningitic E. coli-induced neuroinflammation. Conclusion Our work revealed the effect of TGF beta 1 antagonism on E. coli-induced BBB immune response and suggested that activation of HH signaling may be a potential protective strategy for future bacterial meningitis therapy.
更多查看译文
关键词
TGF beta 1,Hedgehog signaling,SAG,Brain microvascular endothelial cells,miR-155,Neuroinflammation,Escherichia coli
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要