This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krieglstein, C. F. Articles by Granger, D. N. Search for Related Content PubMed PubMed Citation Articles by Krieglstein, C. F. Articles by Granger, D. N.

(American Journal of Pathology. 2007;170:490-496.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060594

Role of Blood- and Tissue-Associated Inducible Nitric-Oxide Synthase in Colonic Inflammation

Christian F. Krieglstein^*, Christoph Anthoni^*, Wolfgang H. Cerwinka, Karen Y. Stokes, Janice Russell, Matthew B. Grisham and D. Neil Granger

From the Department of General Surgery,^* Westfalian Wilhelm’s University, Muenster, Germany; the Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana; and the Department of Urology, University of Miami Miller School of Medicine, Miami, Florida

There is evidence that inducible nitric-oxide synthase (iNOS)-derived NO contributes to the pathophysiology of intestinal inflammation. The aims of this study were to assess the role of iNOS in the development of dextran sodium sulfate (DSS)-induced colonic inflammation and to define the contribution of tissue-specific iNOS expression to this inflammatory response. Study groups included: 1) wild-type (WT) mice; 2) WTWT bone marrow chimeras with normal iNOS function; 3) WTiNOS^–/– chimeras (with functional blood cell iNOS, but iNOS-deficient tissue); 4) iNOS^–/–WT chimeras (with iNOS-deficient blood cells, but normal tissue iNOS activity); and 5) iNOS-deficient mice. In WT mice and WTWT chimeras, DSS-induced colonic inflammation was characterized by bloody diarrhea and a high disease activity index. However, WTiNOS^–/– and iNOS^–/–WT chimeras and iNOS^–/– mice exhibited an attenuated disease activity index, with parallel changes in histopathology. Colonic myeloperoxidase (MPO) was comparably elevated in DSS-treated WT mice (30.1 ± 1.7) and WTWT chimeras (29.0 ± 1), whereas MPO was significantly reduced in iNOS^–/– mice and iNOS^–/–WT chimeras (9.5 ± 1.7 and 15.6 ± 2.2, respectively). WTiNOS^–/– chimeras exhibited the lowest MPO activity (3.7 ± 0.6). Our findings implicate both blood cell- and tissue-derived iNOS in DSS-induced colonic inflammation, with tissue-associated iNOS making a larger contribution to the recruitment of inflammatory cells.

This article has been cited by other articles:

				A. T. Vieira, C. T. Fagundes, A. L. Alessandri, M. G.M. Castor, R. Guabiraba, V. O. Borges, K. D. Silveira, E. L.M. Vieira, J. L. Goncalves, T. A. Silva, et al. Treatment with a Novel Chemokine-Binding Protein or Eosinophil Lineage-Ablation Protects Mice from Experimental Colitis Am. J. Pathol., December 1, 2009; 175(6): 2382 - 2391. [Abstract] [Full Text] [PDF]

				E. Miyauchi, H. Morita, and S. Tanabe Lactobacillus rhamnosus alleviates intestinal barrier dysfunction in part by increasing expression of zonula occludens-1 and myosin light-chain kinase in vivo J Dairy Sci, June 1, 2009; 92(6): 2400 - 2408. [Abstract] [Full Text] [PDF]

				J. H. Chidlow Jr., D. Shukla, M. B. Grisham, and C. G. Kevil Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G5 - G18. [Abstract] [Full Text] [PDF]