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Infection and Immunity, May 2001, p. 3382-3388, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.3382-3388.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Amebic Infection in the Human Colon Induces Cyclooxygenase-2

William F. Stenson,1,* Zhi Zhang,2 Terrence Riehl,1 and Samuel L. Stanley Jr.2

Divisions of Gastroenterology1 and Infectious Diseases,2 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri

Received 27 December 2000/Returned for modification 11 February 2001/Accepted 20 February 2001

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 E2 (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 PGE2 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.

* Corresponding author. Mailing address: Division of Gastroenterology, Campus Box 8124, Washington University School of Medicine, St. Louis, MO 63110. Phone: (314) 362-8940. Fax: (314) 362-8959. E-mail: wstenson{at}im.wustl.edu.

Infection and Immunity, May 2001, p. 3382-3388, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.3382-3388.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Zhang, X., Zhang, Z., Alexander, D., Bracha, R., Mirelman, D., Stanley, S. L. Jr. (2004). Expression of Amoebapores Is Required for Full Expression of Entamoeba histolytica Virulence in Amebic Liver Abscess but Is Not Necessary for the Induction of Inflammation or Tissue Damage in Amebic Colitis. Infect. Immun. 72: 678-683 [Abstract] [Full Text]  
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