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Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases

Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases
Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases
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 A(4) hydrolase (P = 0.004), which make up the biosynthetic pathway of the potent neutrophil chemotaxin leukotriene B(4). Immunoexpression of the leukotriene C(4) synthase was unaltered (P > 0.2). The increased representation of leukotriene B(4)-pathway enzymes was associated with higher counts of neutrophils (P = 0.0001), macrophages (P = 0.03), eosinophils (P = 0.0004), CD8(+) T cells (P 0.9). 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 B(4), 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.
inflammatory bowel disease, ulcerative colitis, Crohn's disease, leukotriene B4, 5-lipoxygenase, cyclooxygenase
537-546
Jupp, James
3a76c4fe-18d3-4c65-91c2-5258a7b0c183
Hillier, Keith
1f61949a-4d18-4166-b161-afcedf46b4c8
Elliott, Daniel H.
51156cef-9ea8-47f2-805c-1d7cc03706ad
Fine, David R.
ce3d6a77-040e-4aec-a8f5-4c4c22431605
Bateman, Adrian C.
28ae82e3-b93a-429a-81f5-04e8f1ff4cc7
Johnson, Penny A.
2222bc26-0e15-40af-a7a5-c46dbb64c66b
Cazaly, Angelica M.
4e1ff9bd-34e3-436f-8624-d1b85626f6eb
Penrose, John F.
a1d34fbc-ff46-49bd-a184-ba20a900239b
Sampson, Anthony P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Jupp, James
3a76c4fe-18d3-4c65-91c2-5258a7b0c183
Hillier, Keith
1f61949a-4d18-4166-b161-afcedf46b4c8
Elliott, Daniel H.
51156cef-9ea8-47f2-805c-1d7cc03706ad
Fine, David R.
ce3d6a77-040e-4aec-a8f5-4c4c22431605
Bateman, Adrian C.
28ae82e3-b93a-429a-81f5-04e8f1ff4cc7
Johnson, Penny A.
2222bc26-0e15-40af-a7a5-c46dbb64c66b
Cazaly, Angelica M.
4e1ff9bd-34e3-436f-8624-d1b85626f6eb
Penrose, John F.
a1d34fbc-ff46-49bd-a184-ba20a900239b
Sampson, Anthony P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60

Jupp, James, Hillier, Keith, Elliott, Daniel H., Fine, David R., Bateman, Adrian C., Johnson, Penny A., Cazaly, Angelica M., Penrose, John F. and Sampson, Anthony P. (2007) Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases. Inflammatory Bowel Diseases, 13 (5), 537-546. (doi:10.1002/ibd.20094).

Record type: Article

Abstract

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 A(4) hydrolase (P = 0.004), which make up the biosynthetic pathway of the potent neutrophil chemotaxin leukotriene B(4). Immunoexpression of the leukotriene C(4) synthase was unaltered (P > 0.2). The increased representation of leukotriene B(4)-pathway enzymes was associated with higher counts of neutrophils (P = 0.0001), macrophages (P = 0.03), eosinophils (P = 0.0004), CD8(+) T cells (P 0.9). 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 B(4), 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.

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More information

Published date: May 2007
Keywords: inflammatory bowel disease, ulcerative colitis, Crohn's disease, leukotriene B4, 5-lipoxygenase, cyclooxygenase

Identifiers

Local EPrints ID: 59345
URI: http://eprints.soton.ac.uk/id/eprint/59345
PURE UUID: aed6f02a-a1a7-41bf-82cb-97e4a9fd650b
ORCID for Anthony P. Sampson: ORCID iD orcid.org/0009-0008-9653-8935

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Date deposited: 02 Sep 2008
Last modified: 16 Mar 2024 02:51

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Contributors

Author: James Jupp
Author: Keith Hillier
Author: Daniel H. Elliott
Author: David R. Fine
Author: Adrian C. Bateman
Author: Penny A. Johnson
Author: Angelica M. Cazaly
Author: John F. Penrose

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