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Mechanisms of Active Intestinal Inflammation and Potential Down-Regulation Via Lipoxins

  • Andrew T. Gewirtz
  • Andrew S. Neish
  • James L. Madara
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)

Abstract

Chronic inflammatory diseases of the intestine (i.e. Crohn’s and chronic ulcerative colitis-collectively known as inflammatory bowel disease [IBDI) are a very significant public health problem in the United States and other industrialized nations. Thus, effort has been made toward understanding the biological mechanisms that regulate such inflammation. Largely, these efforts have focused on identifying the mechanisms that mediate activation of inflammation and have succeeded in identifying a variety of signaling pathways by which a wide range of agonists can activate a mucosal immune inflammatory response. Playing a central role in many of these pathways is the intestinal epithelium, which serves as a barrier to, and interfaces with the outside world. However, recent studies have shown that not only can some agonists activate pro-inflammatory signals in intestinal epithelial cells, but other agonists can activate “anti-inflammatory” signals in these cells that dampen the responses to pro-inflammatory agonists. One such anti-inflammatory agonist is the eicosanoid lipoxin A4 (LXA4). Specifically, LXA4its epimer 15-LXA4and their analogs potently down-regulate defining and causative events of intestinal inflammation in an in vitro model. These compounds are now being tested for their ability to down-regulate inflammation in mouse models of colitis and may ultimately prove to be of significant benefit to individuals suffering from debilitating chronic inflammatory intestinal disorders.

Keywords

Inflammatory Bowel Disease Intestinal Epithelial Cell Intestinal Epithelium Intestinal Inflammation Stable Analog 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Andrew T. Gewirtz
    • 1
  • Andrew S. Neish
    • 1
  • James L. Madara
    • 1
  1. 1.Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory MedicineEmory University School of MedicineAtlanta

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