Effects of B7-H3 on the inflammatory response and expression of MMP-9 in mice with pneumococcal meningitis.
B7-H3, a new member of the B7 superfamily, plays a key role in the regulation of T cell-mediated immune responses. Our previous work showed that B7-H3 strongly augmented both LPS- and bacterial lipoprotein-induced NF-κB activation and inflammatory response, and soluble B7-H3 was elevated in CSF and plasma of patients with bacterial meningitis. MMP-9 has been implicated in blood-brain barrier disruption, inflammation, and vasculitis during the pathogenesis of bacterial meningitis. In this study, we report that in a murine model of pneumococcal meningitis, B7-H3 treatment enhances inflammatory response in the meninges, upregulates MMP-9 expression in cerebral parenchyma, and deteriorates clinical disease status indicated by weight loss and impaired movement ability. In vitro results showed that B7-H3 augmented MMP-9 secretion from Streptococcus pneumoniae-stimulated microglia cells. Thus, our data indicate that B7-H3 contributes to the development of pneumococcal meningitis by exaggerating inflammatory responses and upregulating MMP-9 activity in CNS, which ultimately lead to neuronal injury.
Department of Neurology, Affiliated Children's Hospital, Soochow University, Suzhou 215003, China. xuqinlili@yahoo.com
Xuqin
X
Chen
Yanhui
Y
Bai
Weili
W
Cui
Zhedong
Z
Wang
Guangbo
G
Zhang
Yunyun
Y
Xu
Xueming
X
Zhu
Yan
Y
Li
Jiang Huai
JH
Wang
D000818:Animals; D060887:B7 Antigens / Q000633:toxicity*; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008578:Meninges / Q000276:immunology / Q000378:metabolism; D008586:Meningitis, Pneumococcal / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009068:Movement; D014158:Transcription, Genetic; D015431:Weight Loss
D060887:B7 Antigens; C486038:Cd276 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse