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5-lipoxygenase modulates the alteration of paracellular barrier function in mice ileum during experimental colitis.
Shock. 2006 Apr; 25(4):377-83.S

Abstract

Small intestine permeability is frequently altered in inflammatory bowel disease and may be caused by the translocation of intestinal toxins through leaky small intestine tight junctions (TJs) and adherence. Recently, it has been shown that 5-lipoxygenase (5-LO) plays an important role in the development of various inflammatory conditions like inflammatory bowel disease. In the present study, by comparing the responses in wild-type mice (5-LOWT) with those of mice lacking the 5-lipoxygenase (5-LOKO), we investigated the role played by this enzyme in the permeability and structure of small intestine TJs in an animal model of experimental colitis. To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). Four days after colitis induction by DNBS, the ileal TJs were studied by means of transmission electron microscopy using lanthanum nitrate and immunohistochemistry of occludin and ZO-1. When compared with DNBS-treated 5-LOWT mice, DNBS-treated 5-LOKO mice experienced a reduced rate of the extent and severity of the histological signs of colon injury. After administration of DNBS, 5-LOWT mice showed a significant increase of ileal permeability (88.3% +/- 1.2%) compared with sham (5.6% +/- 0.5%). In colitis, the percentage of "leaky" junctions in terminal ilea correlated positively with the macroscopic colon damage score. Distal colitis in 5-LOWT mice induces an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. On the contrary, a significant reduction of (1) the degree of colon injury, (2) the alteration of ZO-1 and occludin localization (immunohistochemistry), and (3) ileal permeability (8.1% +/- 0.7%) caused by DNBS in the colon was observed in 5-LOKO mice. Similarly, the treatment of 5-LOWT with zileuton (50 mg/kg per oral gavage twice a day), a 5-LO inhibitor, resulted in a significant reduction of all the previously described parameters. Taken together, our results clearly demonstrate that 5-LO modulates small intestinal permeability in experimental colitis through the regulation of TJ protein.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica, Policlinico Universitario, Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16670640

Citation

Mazzon, Emanuela, et al. "5-lipoxygenase Modulates the Alteration of Paracellular Barrier Function in Mice Ileum During Experimental Colitis." Shock (Augusta, Ga.), vol. 25, no. 4, 2006, pp. 377-83.
Mazzon E, Sautebin L, Caputi AP, et al. 5-lipoxygenase modulates the alteration of paracellular barrier function in mice ileum during experimental colitis. Shock. 2006;25(4):377-83.
Mazzon, E., Sautebin, L., Caputi, A. P., & Cuzzocrea, S. (2006). 5-lipoxygenase modulates the alteration of paracellular barrier function in mice ileum during experimental colitis. Shock (Augusta, Ga.), 25(4), 377-83.
Mazzon E, et al. 5-lipoxygenase Modulates the Alteration of Paracellular Barrier Function in Mice Ileum During Experimental Colitis. Shock. 2006;25(4):377-83. PubMed PMID: 16670640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-lipoxygenase modulates the alteration of paracellular barrier function in mice ileum during experimental colitis. AU - Mazzon,Emanuela, AU - Sautebin,Lidia, AU - Caputi,Achille P, AU - Cuzzocrea,Salvatore, PY - 2006/5/4/pubmed PY - 2008/2/2/medline PY - 2006/5/4/entrez SP - 377 EP - 83 JF - Shock (Augusta, Ga.) JO - Shock VL - 25 IS - 4 N2 - Small intestine permeability is frequently altered in inflammatory bowel disease and may be caused by the translocation of intestinal toxins through leaky small intestine tight junctions (TJs) and adherence. Recently, it has been shown that 5-lipoxygenase (5-LO) plays an important role in the development of various inflammatory conditions like inflammatory bowel disease. In the present study, by comparing the responses in wild-type mice (5-LOWT) with those of mice lacking the 5-lipoxygenase (5-LOKO), we investigated the role played by this enzyme in the permeability and structure of small intestine TJs in an animal model of experimental colitis. To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). Four days after colitis induction by DNBS, the ileal TJs were studied by means of transmission electron microscopy using lanthanum nitrate and immunohistochemistry of occludin and ZO-1. When compared with DNBS-treated 5-LOWT mice, DNBS-treated 5-LOKO mice experienced a reduced rate of the extent and severity of the histological signs of colon injury. After administration of DNBS, 5-LOWT mice showed a significant increase of ileal permeability (88.3% +/- 1.2%) compared with sham (5.6% +/- 0.5%). In colitis, the percentage of "leaky" junctions in terminal ilea correlated positively with the macroscopic colon damage score. Distal colitis in 5-LOWT mice induces an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. On the contrary, a significant reduction of (1) the degree of colon injury, (2) the alteration of ZO-1 and occludin localization (immunohistochemistry), and (3) ileal permeability (8.1% +/- 0.7%) caused by DNBS in the colon was observed in 5-LOKO mice. Similarly, the treatment of 5-LOWT with zileuton (50 mg/kg per oral gavage twice a day), a 5-LO inhibitor, resulted in a significant reduction of all the previously described parameters. Taken together, our results clearly demonstrate that 5-LO modulates small intestinal permeability in experimental colitis through the regulation of TJ protein. SN - 1073-2322 UR - https://www.unboundmedicine.com/medline/citation/16670640/5_lipoxygenase_modulates_the_alteration_of_paracellular_barrier_function_in_mice_ileum_during_experimental_colitis_ L2 - https://doi.org/10.1097/01.shk.0000209530.30564.22 DB - PRIME DP - Unbound Medicine ER -