| First Author | Chi F | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 9 | Pages | e25016 |
| PubMed ID | 21966399 | Mgi Jnum | J:177659 |
| Mgi Id | MGI:5295799 | Doi | 10.1371/journal.pone.0025016 |
| Citation | Chi F, et al. (2011) Meningitic Escherichia coli K1 penetration and neutrophil transmigration across the blood-brain barrier are modulated by alpha7 nicotinic receptor. PLoS One 6(9):e25016 |
| abstractText | Alpha7 nicotinic acetylcholine receptor (nAChR), an essential regulator of inflammation, is abundantly expressed in hippocampal neurons, which are vulnerable to bacterial meningitis. However, it is unknown whether alpha7 nAChR contributes to the regulation of these events. In this report, an aggravating role of alpha7 nAChR in host defense against meningitic E. coli infection was demonstrated by using alpha7-deficient (alpha7(-/-)) mouse brain microvascular endothelial cells (BMEC) and animal model systems. As shown in our in vitro and in vivo studies, E. coli K1 invasion and polymorphonuclear neutrophil (PMN) transmigration across the blood-brain barrier (BBB) were significantly reduced in alpha7(-/-) BMEC and alpha7(-/-) mice. Stimulation by nicotine was abolished in the alpha7(-/-) cells and animals. The same blocking effect was achieved by methyllycaconitine (alpha7 antagonist). The tight junction molecules occludin and ZO-1 were significantly reduced in the brain cortex of wildtype mice infected with E. coli and treated with nicotine, compared to alpha7(-/-) cells and animals. Decreased neuronal injury in the hippocampal dentate gyrus was observed in alpha7(-/-) mice with meningitis. Proinflammatory cytokines (IL-1beta, IL-6, TNFalpha, MCP-1, MIP-1alpha, and RANTES) and adhesion molecules (CD44 and ICAM-1) were significantly reduced in the cerebrospinal fluids of the alpha7(-/-) mice with E. coli meningitis. Furthermore, alpha7 nAChR is the major calcium channel for nicotine- and E. coli K1-increased intracellular calcium concentrations of mouse BMEC. Taken together, our data suggest that alpha7 nAChR plays a detrimental role in the host defense against meningitic infection by modulation of pathogen invasion, PMN recruitment, calcium signaling and neuronal inflammation. |
