A Role of CC Chemokines on the Pathogenesis of Herpes Simplex Encephalomyelitis

CC趋化因子在单纯疱疹性脑脊髓炎发病机制中的作用

基本信息

批准号：
13670675
负责人：
NAKAJIMA Hideto
金额：
$ 1.6万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670675/
关键词：
herpes simplex virus encephalomyelitis chemokine Th1 Th2 cytokines Th2サイトカン

项目摘要

Th1/Th2 responses play an important role on the host defense against herpes simplex encephalomyelitis. Recently, some specific chemokines have been described as an initiator of Th1/Th2 responses. We investigated a role of monocyte chemoattractant protein (MCP)-1 in the pathogenesis of herpesvirus-induced encephalomyelitis (HSM). Anti-MCP-1 antibody greatly decreased HSM severity in mice infected with herpes simplex virus type 2 (HSM mice). HSM severity was markedly enhanced in mice previously treated with a mixture of interleukin (IL) 4 and -10. In response to stimulation with antigen, HSM mouse cells isolated from cerebrospinal fluids (CSF cells) produced IL-4 in culture fluids, however, IL-4 production decreased in CSF cells derived from HSM mice previously treated with anti-MCP-1 antibody. A macrophage population isolated in CSF cells from HSM mice (CSF-Mphi) produced MCP-1 in culture fluids. In response to stimulation with herpesvirus antigen, T cells isolated from CSF cells from HSM mice (CSF-T cells) produced IL-4 into their culture fluids, although MCP-1 was not produced by CSF-T cells. IL-4 production by CSF-T cells was markedly enhanced when they were stimulated with viral antigen in the presence of murine recombinant MCP-1 (rMCP-1). Furthermore, IL-4 was produced in naive splenic T cells cocultured with CSF-Mphi. These results indicate that the severity of HSM is influenced by MCP-1, which stimulates Th2 responses.

TH1/TH2反应在针对单纯疱疹脑脊髓炎的宿主防御中起着重要作用。最近，一些特定的趋化因子被描述为Th1/Th2响应的引发剂。我们研究了单核细胞趋化蛋白（MCP）-1在疱疹病毒诱导的脑脊髓炎（HSM）的发病机理中的作用。抗MCP-1抗体大大降低了被单纯疱疹病毒2型（HSM小鼠）感染的小鼠的HSM严重程度。在先前用白介素（IL）4和-10混合物处理的小鼠中，HSM严重程度显着提高。响应于抗原刺激，从培养液中产生IL-4的脑脊液（CSF细胞）中分离出的HSM小鼠细胞，但是，源自先前用抗MCP-1抗体治疗的HSM小鼠的CSF细胞中IL-4产生降低。来自HSM小鼠（CSF-MPHI）在CSF细胞中分离的巨噬细胞种群在培养液中产生MCP-1。为了用疱疹病毒抗原的刺激，从HSM小鼠（CSF-T细胞）中分离出从CSF细胞中分离出的T细胞将IL-4产生到其培养液中，尽管MCP-1不是由CSF-T细胞产生的。在存在鼠重组MCP-1（RMCP-1）的情况下，用病毒抗原刺激CSF-T细胞产生的IL-4产生。此外，在与CSF-MPHI共培养的天真脾脏T细胞中产生IL-4。这些结果表明，HSM的严重程度受到MCP-1的影响，MCP-1刺激TH2反应。