Activated intestinal macrophages in patients with cirrhosis release NO and IL- 6 that may disrupt intestinal barrier function

Show simple item record Du Plessis, Johannie Vanheel, Hanne Janssen, Carl E.I. Roos, Leonie Slavik, Tomas Stivaktas, Paraskevi Irene Nieuwoudt, Martin J. Van Wyk, Stefan George Vieira, Warren Antonio Pretorius, Etheresia Beukes, Mervyn Farré, Ricard Tack, Jan Laleman, Wim Fevery, Johan Nevens, Frederik Roskams, Tania Van der Merwe, Schalk Willem 2014-10-09T08:14:57Z 2014-10-09T08:14:57Z 2013-06
dc.description.abstract BACKGROUND & AIMS : Bacterial infections commonly occur in decompensated cirrhosis resulting from bacterial translocation from the intestine. We studied the role of intestinal macrophages and the epithelial barrier in cirrhosis. METHODS : Forty-four patients with NASH/ASH cirrhosis (decompensated n = 29, compensated n = 15) and nineteen controls undergoing endoscopy were recruited. Serum was obtained and LPS and LBP levels determined. Intestinal macrophages were characterized by flow cytometry, immunohistochemistry, and nitric oxide (NO) production measured in supernatant of cultured duodenal samples. Quantitative RT-PCR was performed on duodenal biopsies assessing 84 inflammatory genes. Protein levels of cytokines/chemokines were assessed in serum and supernatant. The duodenal wall was assessed by electron microscopy, tight junction protein expression determined by RT-PCR, immunohistochemistry, and Western blot and, functional analysis performed by transepithelial resistance measurement and permeability studies.RESULTS : Increased plasma LPS, LBP levels and higher numbers of duodenal CD33+/CD14+/Trem-1+ macrophages, synthesizing iNOS and secreting NO were present in decompensated cirrhosis. Upregulation of IL-8, CCL2, CCL13 at the transcriptional level, and increased IL-8, and IL-6 were detected in supernatant and serum in cirrhosis. IL-6 and IL-8 co-localised with iNOS+ and CD68+, but not with CD11c+ cells. Electron microscopy demonstrated an intact epithelial barrier. Increased Claudin-2 was detected by Western blot and immunohistochemistry, while decreased transepithelial resistance and increased duodenal permeability were detected in decompensated cirrhosis. CONCLUSIONS : Our study shows the presence of activated CD14+- Trem-1+iNOS+ intestinal macrophages, releasing IL-6, NO, and increased intestinal permeability in patients with cirrhosis, suggesting that these cells may produce factors capable of enhancing permeability to bacterial products. en_US
dc.description.librarian hb2014 en_US
dc.description.uri en_US
dc.identifier.citation Du Plessis, J, Vanheel, H, Janssen, CEI, Roos ,L, Slavik, T, Stivaktas, PI, Nieuwoudt, M, Van Wyk, SG, Vieira, W, Pretorius, E, Beukes, M, Farré, R, Tack, J, Laleman, W, Fevery, J, Nevens, F, Roskams & Van der Merwe, SW 2013, ' Activated intestinal macrophages in patients with cirrhosis release NO and IL- 6 that may disrupt intestinal barrier function', Journal of Hepatology, vol. 58, no. 6, pp. 1125-1132. en_US
dc.identifier.issn 0168-8278 (print)
dc.identifier.issn 1600-0641 (online)
dc.identifier.other 10.1016/j.jhep.2013.01.038
dc.language.iso en en_US
dc.publisher Elsevier en_US
dc.rights © 2013 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Journal of Hepatology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Hepatology, vol. 58, no. 6, pp. 1125-1132, 2013. doi : 10.1016/j.jhep.2013.01.038. en_US
dc.subject Bacterial translocation en_US
dc.subject Intestinal macrophages en_US
dc.subject Epithelial barrier en_US
dc.subject IL-6 en_US
dc.subject Cirrhosis en_US
dc.subject Nitric oxide (NO) en_US
dc.title Activated intestinal macrophages in patients with cirrhosis release NO and IL- 6 that may disrupt intestinal barrier function en_US
dc.type Postprint Article en_US

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