Macrophage-secreted products induce a phenotypic change in hepatocytes: Implications for fibrogenesis

Melino, M., Powell, E. E., Gadd, V. L., Skoien, R., Walker, G., Clouston, A. D. and Jonsson, J. R. (2010). Macrophage-secreted products induce a phenotypic change in hepatocytes: Implications for fibrogenesis. In: Abstracts of: Australian Gastroenterology Week 2010. AGW2010: Australian Gastroenterology Week 2010, Gold Coast, QLD, Australia, (A4-A5). 20-23 October, 2010. doi:10.1111/j.1440-1746.2010.06450.x


Author Melino, M.
Powell, E. E.
Gadd, V. L.
Skoien, R.
Walker, G.
Clouston, A. D.
Jonsson, J. R.
Title of paper Macrophage-secreted products induce a phenotypic change in hepatocytes: Implications for fibrogenesis
Conference name AGW2010: Australian Gastroenterology Week 2010
Conference location Gold Coast, QLD, Australia
Conference dates 20-23 October, 2010
Proceedings title Abstracts of: Australian Gastroenterology Week 2010   Check publisher's open access policy
Journal name Journal of Gastroenterology and Hepatology   Check publisher's open access policy
Place of Publication Richmond, VIC, Australia
Publisher Wiley-Blackwell Publishing Asia
Publication Year 2010
Sub-type Published abstract
DOI 10.1111/j.1440-1746.2010.06450.x
ISSN 0815-9319
Volume 25
Issue Supplement s3
Start page A4
End page A5
Total pages 2
Collection year 2011
Language eng
Formatted Abstract/Summary
Liver macrophages (Kupffer cells) play a key role in the progression of liver injury however their infl uence on hepatocyte function and viability remains unknown. The aim of this study was to investigate whether  macrophage-secreted products alter the phenotype of these epithelial cells. Macrophages were differentiated from THP-1 cells (monocyte cell line) via phorbol myristate acetate stimulation. The resulting macrophage-conditioned
media (MΦCM) was added to two different hepatocyte cell lines, HepG2 and Huh7. Expression of the EMT markers E-cadherin, vimentin, S100A4, collagen, transforming growth factor-β (TGF-β) and α-smooth muscle actin (αSMA) were measured using real-time PCR and immunofl uorescence. Comparisons between untreated and MΦCM-treated cells were analysed using a one-way ANOVA and Tukey’s multiple comparison test. A p value of <0.05 was considered statistically signifi cant. Hepatocytes treated with MΦCM for 24 h acquired mesenchymal-like properties, with reduced E-cadherin (p < 0.05) and enhanced TGF-β (p < 0.001) mRNA expression. Huh7 and HepG2 cells demonstrated partial EMT due to the signifi cant increase in mesenchymal markers, vimentin (p < 0.05) and S100A4 (p < 0.001) respectively. However αSMA and
collagen, two markers associated with complete EMT, showed no signifi - cant change. Interestingly, hepatocyte phenotypic changes were transient as reversal of the mesenchymal-like properties was seen following a further 7 days in culture in normal media.  No change in gene expression was observed in hepatocytes treated with
conditioned media isolated from undifferentiated THP-1 cells. This in vitro study provides evidence that macrophage-secreted products can induce transient phenotypic changes in hepatocytes that may contribute to fi brogenesis. Importantly, the data raise the possibility that hepatocytes may contribute to TGF-β production during infl ammatory liver injury with recruitment and activation of liver macrophage populations.
Q-Index Code EX
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Special Issue: Australian Gastroenterology Week 2010. Published under "Basic Science".

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Created: Sun, 09 Jan 2011, 00:04:15 EST