Selective inhibition of COX-2 is beneficial to mice infected intranasally with VSV
Selective inhibition of COX-2 is beneficial to mice infected intranasally with VSV
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DOI：
10.1016/s0090-6980(01)00185-x
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发表时间：
2002-02-01
影响因子：
2.9
通讯作者：
Reiss, CS
中科院分区：
文献类型：
--
作者：
Chen, NN;Restivo, A;Reiss, CS
环氧合酶(COX)是前列腺素(PG)合成的关键酶。PGS是许多重要的生理和炎症反应的中介体。COX-1和COX-2有两种亚型，它们都在中枢神经系统(CNS)有结构性表达。研究表明，COX-1和COX-2参与了大脑的生理和病理状态。然而，关于COX(S)在中枢神经系统抵抗病毒感染的宿主防御系统中的作用，人们知之甚少。在本报告中，我们使用水泡性口炎病毒诱导的急性脑炎来区分这两种亚型的贡献(S)。COX-2选择性药物塞来昔布(Celebrex(TM))抑制COX-2活性，SC560拮抗COX-1。我们发现，抑制COX-2导致病毒滴度下降，而COX-1拮抗剂在感染后第一天没有同样的效果。塞来昔布抑制组小鼠中枢5-脂氧合酶(5-LO)表达增加，中性粒细胞募集增加。此外，接受塞来昔布治疗的小鼠表达了更多的一氧化氮合酶-1(NOS-1)，这是限制VSV传播的先天免疫系统的关键组成部分。在塞来昔布治疗的小鼠中，1型细胞因子-干扰素-γ和IL-12的表达也增加。(C)2002 Elsevier Science Inc.保留所有权利。
Cyclooxygenase (COX) is the key enzyme for prostaglandin (PG) synthesis. PGs are mediators of many critical physiological and inflammatory responses. There are two isoforms, COX-1 and COX-2, both of which are constitutively expressed in the central nervous system (CNS). Studies have shown that COX-1 and COX-2 are involved in physiological and pathological conditions of the brain. However, little is known about the role(s) of COX in the host defense system against a viral infection in the CNS. In this report, we used Vesicular Stomatitis Virus (VSV) induced acute encephalitis to distinguish between the contribution(s) of the two isoforms. COX-2 activity was inhibited with a COX-2 selective drug, celecoxib (Celebrex(TM)), and COX-1 was antagonized with SC560. We found that inhibition of COX-2 led to decreased viral titers, while COX-1 antagonism did not have the same effect at day I post infection. 5-lipooxygenase (5-LO) expression and neutrophil recruitment in the CNS were increased in celecoxib-inhibited mice. Furthermore, mice treated with celecoxib expressed more Nitric Oxide Synthase-1 (NOS-1), a crucial component of the innate immune system in the restriction of VSV propagation. The expression of type 1 cytokines, IFN-gamma and IL-12, were also increased in celecoxib-treated mice. (C) 2002 Elsevier Science Inc. All rights reserved.