AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 1 104-G111, Copyright © 1993 by American Physiological Society

ARTICLES

Induction of epithelial arachidonate 12-lipoxygenase at active sites of inflammatory bowel disease

V. R. Shannon, W. F. Stenson and M. J. Holtzman
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.

To determine if epithelial lipoxygenases are regulated by mucosal inflammation, we examined the distribution of arachidonate 12-lipoxygenase in healthy colonic tissue and in involved and uninvolved sections of colon with inflammatory bowel disease. Immunohistochemistry of formaldehyde-fixed, paraffin-embedded intestinal tissue using two anti-12-lipoxygenase antibodies and indirect biotin-avidin-peroxidase detection demonstrated that, in contrast to tissue from normal colon (n = 8), in which 12-lipoxygenase antigen was undetectable in mucosal epithelial cells, the mucosal and glandular epithelium of inflamed colon in ulcerative colitis (n = 4) or Crohn's disease (n = 4) exhibited markedly positive immunostaining with anti-12-lipoxygenase antibodies. Immunoblotting of whole cell extracts with anti-12-lipoxygenase antibodies showed immunoperoxidase staining of a single protein band that comigrated with purified 12-lipoxygenase (in relative molecular weight: M(r) = 72,000) in mucosal samples from inflamed colon from subjects with ulcerative colitis or Crohn's disease but no comparable band in samples from uninvolved sections of the same colons or from colons of subjects without inflammatory bowel disease. Assays of 12-lipoxygenase activity indicated a corresponding increase in enzymatic activity in the same mucosal samples. The increased levels of 12-lipoxygenase antigen in the mucosal and glandular epithelial cells in regions of colon affected by inflammatory bowel disease, the corresponding increases in 12-lipoxygenase activity, and the absence of detectable 12-lipoxygenase antigen or enzymatic activity in the same cell types in noninflamed colonic tissue all suggest that epithelial cell 12-lipoxygenase is induced by local mediators of colonic inflammation.

This article has been cited by other articles:

				J. F. Collins, Z. Hu, P. N. Ranganathan, D. Feng, L. M. Garrick, M. D. Garrick, and R. W. Browne Induction of arachidonate 12-lipoxygenase (Alox15) in intestine of iron-deficient rats correlates with the production of biologically active lipid mediators Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G948 - G962. [Abstract] [Full Text] [PDF]

				J. F. Di Mari, J. I. Saada, R. C. Mifflin, J. D. Valentich, and D. W. Powell HETEs enhance IL-1-mediated COX-2 expression via augmentation of message stability in human colonic myofibroblasts Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G719 - G728. [Abstract] [Full Text] [PDF]

				H. Ikawa, H. Kamitani, B. F. Calvo, J. F. Foley, and T. E. Eling Expression of 15-Lipoxygenase-1 in Human Colorectal Cancer Cancer Res., January 1, 1999; 59(2): 360 - 366. [Abstract] [Full Text] [PDF]

				J. A. Cornicelli, K. Welch, B. Auerbach, S. J. Feinmark, and A. Daugherty Mouse Peritoneal Macrophages Contain Abundant {omega}-6 Lipoxygenase Activity That Is Independent of Interleukin-4 Arterioscler Thromb Vasc Biol, December 1, 1996; 16(12): 1488 - 1494. [Abstract] [Full Text]