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Altered leukotriene B4 metabolism in colonic mucosa with inflammatory bowel disease
A Ikehata1, N Hiwatashi, Y Kinouchi
1Third Dept. of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Background:
omega-Oxidation is regarded as the major pathway for leukotriene B4 (LTB4) metabolism. Very little is known about it in colonic mucosa with inflammatory bowel disease (IBD).
Methods:
We investigated the metabolic ratio of omega-oxidation to LTB4 biosynthesis in colonic mucosa from patients with IBD and control subjects. After incubation of colonic mucosa with 14C-arachidonic acid and ionophore A23187, we separated LTB4 and its omega-oxidative metabolites by high-performance liquid chromatography.
Results:
The rate of LTB4 omega-oxidation was comparable to the rate of its biosynthesis. The metabolic ratio was significantly decreased in inflamed mucosa with ulcerative colitis.
Conclusions:
LTB4 omega-hydroxylase activity is an important factor in regulating LTB4 level in colonic mucosa, and the increased LTB4 level in inflamed mucosa with IBD, especially ulcerative colitis, is caused by decreased LTB4 omega-hydroxylase activity and increased 5-lipoxygenase activity.