Macrophage secretory products induce an inflammatory phenotype in hepatocytes.

World Journal of Gastroenterology : WJG
Michelle MelinoElizabeth E Powell

Abstract

To investigate the influence of macrophages on hepatocyte phenotype and function. Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophage-conditioned medium on HepG2 mRNA and protein expression determined. The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus (HCV) infection. Conditioned media from macrophages, but not monocytes, induced a transient morphological change in hepatocytes associated with upregulation of vimentin (7.8 ± 2.5-fold, P = 0.045) and transforming growth factor (TGF)-β1 (2.6 ± 0.2-fold, P < 0.001) and downregulation of epithelial cadherin (1.7 ± 0.02-fold, P = 0.017) mRNA expression. Microarray analysis revealed significant upregulation of lipocalin-2 (17-fold, P < 0.001) and pathways associated with inflammation, and substantial downregulation of pathways related to hepatocyte function. In patients with chronic HCV, real-time polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA (F0 1.0 ± 0.3, F1 2.2 ± 0.2, F2 3.0 ± 9.3, F3/4 4.0 ± 0.8, P = 0.003) and protein expression (F1 1.0 ± 0.5, F2 1.3 ± 0.4, F3/4 3.6 ± 0.4, P = 0.014) w...Continue Reading

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Citations

Dec 18, 2012·Liver International : Official Journal of the International Association for the Study of the Liver·Victoria L GaddElizabeth E Powell
Sep 17, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Marnie J WoodAndrew D Clouston
Oct 18, 2015·Journal of Molecular Neuroscience : MN·Z LestanovaJ Bakos
Jul 22, 2014·Liver International : Official Journal of the International Association for the Study of the Liver·Katrin Kienzl-WagnerHerbert Tilg
Apr 18, 2014·Cutaneous and Ocular Toxicology·David Joseph McCannaMaud B Gorbet
Dec 17, 2014·Neuroscience and Biobehavioral Reviews·Mithilesh Kumar JhaKyoungho Suk
Mar 20, 2018·Cell Death & Disease·Cheng-Ta YangShu-Er Chow
Jun 1, 2013·Hepatology International·Carmine Finelli, Giovanni Tarantino
Mar 5, 2021·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Florian PadbergSebastian Zellmer
Jan 2, 2018·Experimental Cell Research·Colin H BeckwittAlan Wells
Jul 4, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Wenzhe SongChristudas Morais

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