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《Journal of Applied Clinical Pediatrics》 2012-17
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B7 Homolog 3 Promote Inflammatory Response and Pathological Injury of Streptococcus Pneumoniae Meningitis via A Toll-Like Receptor 2 Dependent Mechanism in Mice

CHEN Xu-qin1,WANG Jiang-huai2,ZHANG Xue-guang3,BAO Guan-shui4(1.Department of Neurology,Children′s Hospital Affiliated to Soochow University,Suzhou 215003,Jiangsu Province,China;2.Institute of Pediatrics,Children′s Hospital Affiliated to Soochow University,Suzhou 215003,Jiangsu Province,China;3.Institute of Medical Biotechnology,Soochow University,Suzhou 215007,Jiangsu Province,China;4.Department of Neurology,the 3rd People′s Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 201900,China)  
Objective To investigate the impact of B7 homolog 3(B7-H3) on inflammatory response and blood-brain barrier integrity during streptococcus pneumoniae(SP)meningitis,and explore its mechanism. Methods SP meningitis was established by intracerebral ventricular injection of SP suspension.Wild-type mice were randomly divided into 5 groups and received following injections:PBS,SP alone,SP plus recombinant murine B7-H3,SP plus control IgG mAb,or SP plus anti-B7-H3 blocking mAb.Toll-like receptor 2(TLR2)-deficient mice were divided into 3 groups and received PBS,SP alone,or SP plus recombinant murine B7-H3 injection.At 6 h,18 h,and 30 h post infection,mice anesthetized,blood sample in mice eyes and brains were collected,and brain homogenates were prepared.Tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),interleukin-1 beta(IL-1β),and monocyte chemoattractant protein-1(MCP-1) le-vels in serum,and albumin and IgG levels in brain homogenates were assessed by enzyme-linked immunosorbent assay(ELISA). Results 1.In wild-type mice,injection with SP alone and SP plus recombinant murine B7-H3 led to higher TNF-α,IL-6 and MCP-1 levels in serum at 18 h,and higher TNF-α,IL-6,IL-1β and MCP-1 levels in serum at 30 h,as compared with PBS injection group(Pa0.05).Compared with SP injection group,levels of any cytokines in serum at each time point were not changed after SP plus control IgG mAb group(Pa0.05).SP plus recombinant murine B7-H3 injection induced higher MCP-1 level at 18 h,and higher TNF-α and IL-6 levels at 30 h in serum,as compared with SP injection group[MCP-1:(42.010±3.880) ng·L-1 vs(29.620±3.830) ng·L-1;TNF-α:(37.550±3.232) ng·L-1 vs(24.570±2.377) ng·L-1;IL-6:(66.160±5.766) ng·L-1 vs(48.630±4.418) ng·L-1,Pa0.05].2.In SP plus anti-B7-H3 blocking mAb group,at 30 h,TNF-α and IL-6 levels in serum were lower than those in SP injection group[(18.680±1.798) ng·L-1 vs(24.570±2.377) ng·L-1;(37.180±3.150) ng·L-1vs(48.630±4.418) ng·L-1,Pa0.05];injection with SP alone and SP plus recombinant murine B7-H3 led to higher levels of albumin and IgG in serum at 18,30 h,as compared with PBS injection group(Pa0.05).Compared with SP injection group,levels of albumin and IgG in brain at each time point were not changed after SP plus control IgG mAb injection group(Pa0.05).SP plus recombinant murine B7-H3 injection increased albumin level at 18,30 h,and IgG le-vel at 30 h in brain,as compared with SP injection group[albumin:(59.090±4.184) μg·g-1 vs(35.450±4.256) μg·g-1;(59.890±4.701) μg·g-1 vs(43.790±3.508) μg·g-1;IgG:(36.220±2.775) μg·g-1 vs(25.440±2.620) μg·g-1,Pa0.05].In SP plus anti-B7-H3 blocking mAb group,levels of albumin at 18,30 h,and IgG at 30 h in brain were lower than those in SP injection group [Albumin:(20.590±1.720) μg·g-1 vs(35.450±4.256) μg·g-1;(28.650±3.063) μg·g-1 vs(43.790±3.508) μg·g-1;IgG:(17.380±1.595) μg·g-1 vs(25.440±2.620) μg·g-1,Pa0.05].3.In TLR2-deficient mice,SP plus recombinant murine B7-H3 injection failed to further enhance proinflammatory cytokines further,albumin and IgG release in serum and brain homogenates compared with SP injection alone group(Pa0.05). Conclusions B7-H3 enhances inflammatory response and exacerbates blood-brain barrier injury via a TLR2-dependent mechanism during SP meningitis in mice.
【Fund】: 国家自然科学基金(30972718);; 江苏省自然基金(BK2012605);; 江苏省“双创人才”计划基金
【CateGory Index】: R742.9
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【Citations】
Chinese Journal Full-text Database 2 Hits
1 GUO Hu,ZHENG Guo(Department of Neurology,Nanjing Children′s Hospital Affiliated to Nanjing Medical University,Nanjing 210008,Jiangsu Province,China);Management of Community-Acquired Acute Bacterial Meningitis in Children[J];Journal of Applied Clinical Pediatrics;2011-22
2 ZHUO Zhi-hong,WANG Huai-li,WANG Yue,XU Yun-na,LUO Qiang,LIU Yu-feng (Department of Pediatrics,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China);Intervention of Melatonin on Apoptosis in Brain Injury Induced by Pneumolysin of Rats[J];Journal of Applied Clinical Pediatrics;2012-08
【Co-citations】
Chinese Journal Full-text Database 4 Hits
1 GU Wen-chao1,2,SUN Jing1,3,FU Feng-qing1,ZHANG Guang-bo4,ZHOU Ying-hui1,2,ZHANG Xue-guang1,4(1.Medical Biotechnology Institute of Soochow University,Suzhou 215007,China;2.Department of Biochemistry and Molecular Biology of Soochow University,Suzhou 215123,China;3.Suzhou Health Technology College,Suzhou 215009,China;4.Key Laboratory of Clinic Immunology of Jiangsu Province,No.1 Affiliated Hospital,Soochow University,Suzhou 215006,China);The molecular mechanism of inability of human highly repeating 41gB7-H3 molecule to form soluble B7-H3 protein[J];Current Immunology;2011-03
2 BAI Yan-hui1,CHEN Xu-qin1,WANG Zhe-dong1,LI Yan1,CUI Wei-li1,ZHANG Guang-bo2,XUE Jian3(1.Department of Neurology,Children′s Hospital Affiliated to Soochow University,Suzhou 215003,Jiangsu Province,China;2.Clinical Immunology Laboratory,Soochow University First Affiliated Hospital,Suzhou 215000,Jiangsu Province,China;3.Clinical Laboratory,Children′s Hospital Affiliated to Soochow University,Suzhou 215003,Jiangsu Province,China);Changes of B7-H3 and Interleukin-1β Levels in Cerebrospinal Fluid and Serum in Children with Bacterial Meningitis and It′s Clinical Significance[J];Journal of Applied Clinical Pediatrics;2012-12
3 LI Shu-xiang1,ZHANG Guang-bo1,SUN Hai-hong2,GAO Xin1,ZHANG Xue-guang1 1Medical Biotechnology Institute of Soochow University,Suzhou 215007;2Department of Biochemistry and Molecular Biology,School of Medicine,Soochow University,Suzhou 215123,China;Establishment of a sandwich ELISA for testing serum sB7-H3 and detection of sB7-H3 levels in liver disease[J];Chinese Journal of Cellular and Molecular Immunology;2012-01
4 SUN Hai-Hong,ZHANG Guang-Bo,SHI Jin-Fang,LI Shu-Xiang,GU Wen-Chao,SHI Xiao-Rui,ZHOU Ying-Hui,ZHANG Xue-Guang.Institute of Medical Biotechnology,Soochow University,Clinical Immunology Key Laboratory of Jiangsu Province,Suzhou 215007,China;Detection and clinical significance of the soluble B7-H3 in acute leukemia[J];Chinese Journal of Immunology;2012-04
【Secondary Citations】
Chinese Journal Full-text Database 3 Hits
1 GAO Hui-ling1,ZHANG Chen-guang2,ZHU Lin-lin2,HE Zhi-an2;Clinical Significance of Determinations of Serum Procalcitonin,Prealbumin and C-Reactive Protein in Children with Infection Diseases[J];Journal of Applied Clinical Pediatrics;2009-12
2 QI Xu-sheng,PAN Tong-guo,YANG Yu-mei(Medical Treatment Center for Children,Taihe Hospital Affiliated to Yunyang Medical College,Shiyan 442000,Hubei Province,China);Changes of Matrix Metalloproteinase in Serum and Cerebrospinal Fluid of Children with Purulent Meningitis and Those Clinical Significances[J];Journal of Applied Clinical Pediatrics;2010-06
3 QIAO Li-li,SHEN Wei-qin,CHEN Guo-hong,ZHANG Xiao-li(Department of Pediatrics,Songjiang Central Hospital,Shanghai 201600,China);Neuroprotective Role of Melatonin on Hypoxic-Ischemic Brain Damage in Neonatal Rats[J];Journal of Applied Clinical Pediatrics;2011-15
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