Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases
Article first published online: 17 JAN 2007
Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 13, Issue 5, pages 537–546, May 2007
How to Cite
Jupp, J., Hillier, K., Elliott, D. H., Fine, D. R., Bateman, A. C., Johnson, P. A., Cazaly, A. M., Penrose, J. F. and Sampson, A. P. (2007), Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases. Inflamm Bowel Dis, 13: 537–546. doi: 10.1002/ibd.20094
- Issue published online: 6 APR 2007
- Article first published online: 17 JAN 2007
- Manuscript Accepted: 22 NOV 2006
- Manuscript Received: 9 NOV 2006
- Southampton Gastrointestinal Research Fund, a charitable fund administered by the Southampton University Hospitals Trust
- inflammatory bowel disease;
- ulcerative colitis;
- Crohn's disease;
- leukotriene B4;
Background: Leukotrienes derived from the 5-lipoxygenase pathway are proinflammatory lipid mediators that possibly play a role in inflammatory bowel diseases. The expression of 5-lipoxygenase pathway proteins has not previously been examined in colonic mucosa in inflammatory bowel disease.
Results: Quantitative immunohistochemical analyses showed that, compared to those of the control subjects (n = 9), colonic biopsies from patients with active inflammatory bowel disease (n = 17) had 3- to 7-fold higher mean counts of cells expressing 5-lipoxygenase (P = 0.03), 5-lipoxygenase-activating protein (P = 0.005), and the leukotriene A4 hydrolase (P = 0.004), which make up the biosynthetic pathway of the potent neutrophil chemotaxin leukotriene B4. Immunoexpression of the leukotriene C4 synthase was unaltered (P > 0.2). The increased representation of leukotriene B4–pathway enzymes was associated with higher counts of neutrophils (P = 0.0001), macrophages (P = 0.03), eosinophils (P = 0.0004), CD8+ T cells (P < 0.001), activated T cells (P < 0.05), and B cells (P < 0.05) but not of mast cells (P > 0.9). These eicosanoid and cellular changes were most marked in the subgroup of patients with ulcerative colitis (n = 9), and were absent in patients with quiescent disease (n = 6). The anomalies in the 5-lipoxygenase pathway were accompanied as expected by more cells immunostaining for cytokine-inducible COX-2 (P = 0.004, n = 17), but this study also revealed a greater number of cells expressing COX-1 in the samples from the patients in the ulcerative colitis subgroup (P = 0.03, n = 9).
Conclusions: The 5-lipoxygenase data provide a cellular basis for increased tissue synthesis of the leukotriene B4, as reflected in the colonic mucosa and rectal dialysates of patients with active inflammatory bowel disease, which contributes to neutrophil influx and colonic injury. The COX-1/COX-2 data highlight the ambiguous functional role of prostanoid pathways in inflammatory bowel diseases.
(Inflamm Bowel Dis 2007)