Cyclooxygenase-2-mediated prostaglandin E2 production in mesenteric lymph nodes and in cultured macrophages and dendritic cells after infection with Salmonella.
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-1 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.
Bowman
Christal C
CC
Department of Biology, University of North Carolina, Charlotte, NC 28223, USA.
Bost
Kenneth L
KL
D000284:Administration, Oral; D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology / Q000378:metabolism; D000068579:Celecoxib; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D003713:Dendritic Cells / Q000201:enzymology / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008198:Lymph Nodes / Q000201:enzymology / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000378:metabolism; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011720:Pyrazoles; D012333:RNA, Messenger / Q000096:biosynthesis; D012481:Salmonella Infections, Animal / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000276:immunology; D013449:Sulfonamides / Q000008:administration & dosage
D007527:Isoenzymes; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D015232:Dinoprostone