J Hendel1, I Ahnfelt-Rønne, O H Nielsen. 1. Department of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Denmark.
Abstract
BACKGROUND: In inflammatory bowel disease (IBD) the disease activity correlates with colonic concentrations of leukotrienes (LTs). The enzyme 5-lipoxygenase (5-LO) is responsible for the enzymatic production of LTs. It has previously been demonstrated in experimental models of inflammation, that 5-LO is activated through intracellular translocation of the pre-formed enzyme, and increased constitutive activation of 5-LO has been demonstrated in idiopathic pulmonary fibrosis. The objective of the present study was to investigate whether de novo synthesis of 5-LO is increased in patients with quiescent IBD, or is induced during acute exacerbations of IBD. METHODS: Sixty-one individuals were included in the study. Twenty-eight had ulcerative colitis (UC), 21 had Crohn's disease (CD), and 12 were healthy controls. A standard rigid rectoscopy was performed in all individuals. The degree of inflammation was assessed using a semi-quantitative scale. A mucosal biopsy was taken from the most inflamed area as judged macroscopically. mRNA for 5-LO was detected using a RT-PCR technique, and the assay applied was evaluated by control experiments. RESULTS: The expression of mRNA for 5-LO in colonic biopsies was similar in IBD patients with quiescent disease and healthy controls. When grouped according to endoscopically assessed disease activity the fraction of patients demonstrating 5-LO mRNA in colonic biopsies showed no significant change (p > 0,6; chi2 -test for trend). CONCLUSIONS: This study demonstrates no significant relationship between endoscopically assessed disease activity and relative presence of mRNA for 5-LO in colonic biopsies. Thus, there is no evidence of increased expression of 5-LO mRNA in either quiescent or active stages of IBD.
BACKGROUND: In inflammatory bowel disease (IBD) the disease activity correlates with colonic concentrations of leukotrienes (LTs). The enzyme 5-lipoxygenase (5-LO) is responsible for the enzymatic production of LTs. It has previously been demonstrated in experimental models of inflammation, that 5-LO is activated through intracellular translocation of the pre-formed enzyme, and increased constitutive activation of 5-LO has been demonstrated in idiopathic pulmonary fibrosis. The objective of the present study was to investigate whether de novo synthesis of 5-LO is increased in patients with quiescent IBD, or is induced during acute exacerbations of IBD. METHODS: Sixty-one individuals were included in the study. Twenty-eight had ulcerative colitis (UC), 21 had Crohn's disease (CD), and 12 were healthy controls. A standard rigid rectoscopy was performed in all individuals. The degree of inflammation was assessed using a semi-quantitative scale. A mucosal biopsy was taken from the most inflamed area as judged macroscopically. mRNA for 5-LO was detected using a RT-PCR technique, and the assay applied was evaluated by control experiments. RESULTS: The expression of mRNA for 5-LO in colonic biopsies was similar in IBD patients with quiescent disease and healthy controls. When grouped according to endoscopically assessed disease activity the fraction of patients demonstrating 5-LO mRNA in colonic biopsies showed no significant change (p > 0,6; chi2 -test for trend). CONCLUSIONS: This study demonstrates no significant relationship between endoscopically assessed disease activity and relative presence of mRNA for 5-LO in colonic biopsies. Thus, there is no evidence of increased expression of 5-LO mRNA in either quiescent or active stages of IBD.
Authors: Irina Costea; David R Mack; David Israel; Kenneth Morgan; Alfreda Krupoves; Ernest Seidman; Colette Deslandres; Philippe Lambrette; Guy Grimard; Emile Levy; Devendra K Amre Journal: PLoS One Date: 2010-12-20 Impact factor: 3.240