Amebic infection in the human colon induces cyclooxygenase-2.
We sought to determine if infection of the colon with Entamoeba histolytica induces the expression of cyclooxygenase-2 and, if it does, to determine the contribution of prostaglandins produced through cyclooxygenase-2 to the host response to amebic infection. Human fetal intestinal xenografts were implanted subcutaneously in mice with severe combined immunodeficiency and allowed to grow; the xenografts were then infected with E. histolytica trophozoites. Infection with E. histolytica resulted in the expression of cyclooxygenase-2 in epithelial cells and lamina propria macrophages. Infection with E. histolytica increased prostaglandin E(2) (PGE2) levels 10-fold in the xenografts and resulted in neutrophil infiltration, as manifested by an 18-fold increase in myeloperoxidase activity. Amebic infection also induced an 18-fold increase in interleukin 8 (IL-8) production and a >100-fold increase in epithelial permeability. Treatment of the host mouse with indomethacin, an inhibitor of cyclooxygenase-1 and cyclooxygenase-2, or with NS-398, a selective inhibitor of cyclooxygenase-2, resulted in (i) decreased PGE(2) levels, (ii) a decrease in neutrophil infiltration, (iii) a decrease in IL-8 production, and (iv) a decrease in the enhanced epithelial permeability seen with amebic infection. These results indicate that amebic infection in the colon induces the expression of cyclooxygenase-2 in epithelial cells and macrophages. Moreover, prostaglandins produced through cyclooxygenase-2 participate in the mediation of the neutrophil response to infection and enhance epithelial permeability.
Stenson
W F
WF
Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. wstenson@im.wustl.edu
Zhang
Z
Z
Riehl
T
T
Stanley
S L
SL
D000818:Animals; D003106:Colon / Q000201:enzymology* / Q000469:parasitology; D003108:Colonic Diseases / Q000201:enzymology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004749:Entamoebiasis / Q000201:enzymology*; D004790:Enzyme Induction; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*
D007375:Interleukin-1; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D009195:Peroxidase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone