Cyclooxygenase-2-mediated prostaglandin E2 production in mesenteric lymph nodes and in cultured macrophages and dendritic cells after infection with Salmonella
Cyclooxygenase-2-mediated prostaglandin E2 production in mesenteric lymph nodes and in cultured macrophages and dendritic cells after infection with Salmonella
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DOI：
10.4049/jimmunol.172.4.2469
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发表时间：
2004-02-15
影响因子：
4.4
通讯作者：
Bost, KL
中科院分区：
文献类型：
--
作者：
Bowman, CC;Bost, KL
尽管许多研究已经证明肠上皮细胞在感染沙门氏菌野生型菌株后能够产生pg，但很少有研究关注粘膜淋巴组织中沙门氏菌诱导的前列腺素。考虑到pg对宿主反应的深远影响，这是令人惊讶的。为了开始解决粘膜部位PG的产生，小鼠口服接种沙门氏菌，并在感染后不同时间观察环氧化酶-2 (COX-2) mRNA表达和PGE(2)合成。肠系膜淋巴结高度诱导COX-2 mRNA表达，而cox - 1 mRNA表达则是组成性的。暴露于活沙门氏菌后，肠系膜淋巴结中PGE(2)的产生也显著增加，而暴露于死细菌后则没有。这种增加的PGE(2)反应可以被选择性COX-2抑制剂塞来昔布（celecoxib）治疗小鼠阻断。在沙门氏菌病期间用塞来昔布治疗小鼠导致感染后第3天肠系膜淋巴结活菌增加。然而，塞来昔布治疗延长了致命感染动物的存活时间。体外研究表明，沙门氏菌诱导巨噬细胞和树突状细胞上调COX-2 mRNA表达和PGE(2)分泌，塞来昔布也可以阻断这一过程。有趣的是，与暴露于沙门氏菌衍生的LPS相比，将这些培养的apc暴露于活沙门氏菌中对诱导PGE(2)合成的刺激要大得多。本研究表明，感染野生型沙门氏菌后，肠系膜淋巴结、巨噬细胞和树突状细胞可诱导PGE(2)合成。免疫学杂志，2004,32(2):2469-2475。
Although numerous studies have demonstrated the ability of intestinal epithelial cells to produce PGs after infection with wild-type strains of Salmonella, few studies have focused on Salmonella-induced prostanoids in mucosal lymphoid tissues. This is surprising in view of the profound effects PGs can have on the host response. To begin to address PG production at mucosal sites, mice were orally inoculated with Salmonella, and at varying times postinfection cyclooxygenase-2 (COX-2) mRNA expression and PGE(2) synthesis were investigated. COX-2 mRNA expression was highly inducible in the mesenteric lymph nodes, whereas COX-I mRNA levels were constitutive. PGE(2) production also increased significantly in the mesenteric lymph nodes following exposure to viable Salmonella, but not after exposure to killed bacteria. This increased PGE(2) response could be blocked by treatment of mice with the selective COX-2 inhibitor, celecoxib. Treatment of mice with celecoxib during salmonellosis resulted in increased viable bacteria in the mesenteric lymph nodes by day 3 postinfection. However, celecoxib treatment prolonged the survival of lethally infected animals. In vitro studies demonstrated Salmonella-induced up-regulation of COX-2 mRNA expression and PGE(2) secretion by both macrophages and dendritic cells, which could also be blocked in the presence of celecoxib. Interestingly, exposure of these cultured APCs to viable Salmonella was a much greater stimulus for induction of PGE(2) synthesis than exposure to Salmonella-derived LPS. The present study demonstrates induction of PGE(2) synthesis in mesenteric lymph nodes, macrophages, and dendritic cells after infection with wild-type Salmonella. The Journal of Immunology, 2004, 172: 2469-2475.