Nitric Oxide Involved in the IL-1-Induced Inhibition of Fructose Intestinal Transport Alberto Garcı ´a-Barrios, 1,2 Natalia Guille ´n, 2,3 Sonia Gasco ´n, 1,2 Jesu ´ s Osada, 2,3 Carmen M Vazquez, 4 Jose ´ Luis Miguel-Carrasco, 4 and M Jesu ´ s Rodrı ´guez-Yoldi 1,2 * 1 Physiology Unit, Department of Pharmacology and Physiology, Veterinary Faculty, University of Zaragoza, 50013 Zaragoza, Spain 2 CIBER de Fisiopatologı ´a de la Obesidad y Nutricio ´n (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain 3 Biochemistry Unit, Department of Biochemistry and Molecular Biology, Veterinary Faculty, University of Zaragoza, 50013 Zaragoza, Spain 4 Physiology Unit, Department of Physiology and Zoology, Pharmacy Faculty, University of Sevilla, 41012 Sevilla, Spain ABSTRACT Interleukin-1 (IL-1) is a pleiotropic cytokine produced by cells of the immune system and a large variety of other cell types including endothelial cells. It is released during inflammatory and infectious diseases, and possesses a wide spectrum of autocrine, paracrine and endocrine activities. The aim of this work was to examine the IL-1 effect on D-fructose transport across rabbit jejunum and try to identify the mediators implicated in this process. A sepsis condition was induced for 90 min after intravenous (iv) administration of IL-1 and body temperature was recorded. Studies on cellular intestinal integrity have not shown modifications of the epithelium and the basement membrane. D-fructose intestinal transport was studied in rabbit jejunum from control and treated animals and it was reduced in the latter ones. This cytokine decreased both the mucosal to serosal transepithelial flux and the transport across brush-border membrane vesicles of D-fructose. The inhibition was reversed by L-NAME (nitric oxide [NO] synthase inhibitor), but not by indomethacin (cyclooxygenase 1 and 2 inhibitor). Both inhibitors were administered iv 15 min before the IL-1. The protein levels of GLUT5 were not changed in all animal groups and those of mRNA were even increased. In summary, these findings indicate that IL-1, at the time assayed, induced a significant reduction in the relative intrinsic activity of GLUT5 and in this decrease are involved NO signalling pathways. In this way, blockage of D-fructose intestinal uptake by IL-1 may be playing an essential role in the pathophysiology of septic shock. J. Cell. Biochem. 111: 1321–1329, 2010. ß 2010 Wiley-Liss, Inc. KEY WORDS: GLUT5; INTESTINAL TRANSPORT; IL-1b; RABBIT; FRUCTOSE; NO; PROSTAGLANDINS T he intestinal absorption epithelium serves as a dynamic barrier which, under normal conditions, maintains the regulated uptake of nutrients and water while excluding potential pathogens [McKay and Baird, 1999]. A variety of bacteria and their excreted/secreted products have direct effects on epithelial ion transport and permeability and release of cytokines during bacterial infection may impact directly on epithelial function [Lewis et al., 1995; Sears and Kaper, 1996]. There is evidence that immune-derived cytokines can mediate metabolic alterations during the course of infective, inflammatory, autoimmune and neoplastic processes [Powanda and Beisel, 2003; Riedemann et al., 2004], either by acting locally or by interacting with different endocrine mechanisms [Bachmann and Kopf, 2002; Powanda and Beisel, 2003]. Studies at subcellular, cellular and tissues levels allow to investigate how cytokines interact with each other and with non-cytokine neuroimmune mediators to regulate homeostasis in the intestine [McKay and Baird, 1999]. The interleukins (IL) are pleiotropic cytokines that affect a wide variety of cells and they are small soluble mediators that participate in a variety of physiological and pathological events [Church et al., 2007]. IL-1 consists of three members: IL-1a, IL-1b and IL-1 receptor antagonist (IL-1ra). IL-b is secreted into surrounding interstitial fluid and blood circulation during inflammation and mediates wide-ranging proinflammatory actions [Dinarello, 2005, Journal of Cellular Biochemistry ARTICLE Journal of Cellular Biochemistry 111:1321–1329 (2010) 1321 Grant sponsor: FIS; Grant sponsor: ISCIII; Grant number: CB06/03/1012; Grant sponsor: Departamento de Ciencia, Tecnologı ´a y Universidad del Gobierno de Arago ´n (Spain); Grant numbers: A-32, PM051/2007, PI017/09. *Correspondence to: M Jesu ´ s Rodrı ´guez-Yoldi, Physiology Unit, Veterinary Faculty, Miguel Servet 177, 50013 Zaragoza, Spain. E-mail: mjrodyol@unizar.es Received 16 April 2010; Accepted 17 August 2010  DOI 10.1002/jcb.22859  ß 2010 Wiley-Liss, Inc. Published online 27 August 2010 in Wiley Online Library (wileyonlinelibrary.com).