BACKGROUND: Attack by commensal microbiota is one component of induction of inflammatory episodes in ulcerative colitis (UC). In UC, the mucus layer is intrinsically devoid of phosphatidylcholine (PC) resulting in low hydrophobicity which facilitates bacterial invasion. Colonic ectophospholipase-carrying bacterial strains are likely candidates to further thinning the PC mucus barrier and to precipitate inflammatory episodes. OBJECTIVE: To evaluate the effect of phospholipase A2 (PLA2) inhibitors on inflammation in a genetic UC mouse model. METHODS: As PLA2 inhibitor, we applied the bile acid-phospholipid conjugate ursodeoxycholate-lysophosphatidylethanolamide (UDCA-LPE) or as control 5% Tween 80 by oral gavage to intestine-specific kindlin 2 knockout mice. RESULTS: Luminal UDCA-LPE reduced the PLA2 activity in stool by 36 ± 8%. Concomitantly no inflammatory phenotype was observed when compared to kindlin 2(-/-) mice not treated with UDCA-LPE. The improvement was documented in regard to stool consistency, calprotectin levels in stool, and macroscopic/endoscopic as well as histologic features of the mucosa. The pattern of colonic microbiota distribution obtained in the UC phenotype mice was reversed by UDCA-LPE to the control mice pattern. CONCLUSION: The inhibition of the bacterial ectophospholipase A2 activity improves mucosal inflammation in a genetic mouse model of UC. It is assumed that the remaining mucus PC shield is better preserved when luminal PLA2 is suppressed.
BACKGROUND: Attack by commensal microbiota is one component of induction of inflammatory episodes in ulcerative colitis (UC). In UC, the mucus layer is intrinsically devoid of phosphatidylcholine (PC) resulting in low hydrophobicity which facilitates bacterial invasion. Colonic ectophospholipase-carrying bacterial strains are likely candidates to further thinning the PC mucus barrier and to precipitate inflammatory episodes. OBJECTIVE: To evaluate the effect of phospholipase A2 (PLA2) inhibitors on inflammation in a genetic UC mouse model. METHODS: As PLA2 inhibitor, we applied the bile acid-phospholipid conjugate ursodeoxycholate-lysophosphatidylethanolamide (UDCA-LPE) or as control 5% Tween 80 by oral gavage to intestine-specific kindlin 2 knockout mice. RESULTS: Luminal UDCA-LPE reduced the PLA2 activity in stool by 36 ± 8%. Concomitantly no inflammatory phenotype was observed when compared to kindlin 2(-/-) mice not treated with UDCA-LPE. The improvement was documented in regard to stool consistency, calprotectin levels in stool, and macroscopic/endoscopic as well as histologic features of the mucosa. The pattern of colonic microbiota distribution obtained in the UC phenotype mice was reversed by UDCA-LPE to the control mice pattern. CONCLUSION: The inhibition of the bacterial ectophospholipase A2 activity improves mucosal inflammation in a genetic mouse model of UC. It is assumed that the remaining mucus PC shield is better preserved when luminal PLA2 is suppressed.
Authors: Jost Langhorst; Sigrid Elsenbruch; Julia Koelzer; Andreas Rueffer; Andreas Michalsen; Gustav J Dobos Journal: Am J Gastroenterol Date: 2007-10-04 Impact factor: 10.864
Authors: Annika Braun; Irina Treede; Daniel Gotthardt; Anke Tietje; Alexandra Zahn; Rebecca Ruhwald; Ulrike Schoenfeld; Thilo Welsch; Peter Kienle; Gerhard Erben; Wolf-Dieter Lehmann; Joachim Fuellekrug; Wolfgang Stremmel; Robert Ehehalt Journal: Inflamm Bowel Dis Date: 2009-11 Impact factor: 5.325