Original Article
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World J Gastroenterol. May 21, 2013; 19(19): 2883-2893
Published online May 21, 2013. doi: 10.3748/wjg.v19.i19.2883
Regulation of dipeptidyl peptidase 8 and 9 expression in activated lymphocytes and injured liver
Sumaiya Chowdhury, Yiqian Chen, Tsun-Wen Yao, Katerina Ajami, Xin M Wang, Yury Popov, Detlef Schuppan, Patrick Bertolino, Geoffrey W McCaughan, Denise MT Yu, Mark D Gorrell
Sumaiya Chowdhury, Yiqian Chen, Tsun-Wen Yao, Katerina Ajami, Xin M Wang, Patrick Bertolino, Geoffrey W McCaughan, Denise MT Yu, Mark D Gorrell, Centenary Institute and Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia
Yury Popov, Detlef Schuppan, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
Mark D Gorrell, Molecular Hepatology, Centenary Institute, Newtown, Sydney, NSW 2042, Australia
Author contributions: Chowdhury S and Chen Y performed majority of experiments, analyzed and interpreted data; Chowdhury S wrote manuscript; Yao TW and Ajami K performed experiments; Wang XM, Schuppan D, Popov Y and Bertolino P provided consultation; Schuppan D and Popov Y performed part of the experiments; Most studies took place in McCaughan GW’s laboratory; Yu DMT and Gorrell MD designed and supervised and critically revised and reviewed manuscript.
Supported by Australian National Health and Medical Research Council Grant 512282 (to Gorrell MD); Rebecca L Cooper Foundation Equipment Grants (to Gorrell MD); University of Sydney International Scholarship (to Chen Y); Australian Postgraduate Scholarship (to Yao TW); and Grant NIH U19 AI066313 (to Schuppan D)
Correspondence to: Mark D Gorrell, PhD, Associate Professor, Molecular Hepatology, Centenary Institute, Locked Bag No. 6, Newtown, Sydney, NSW 2042, Australia. m.gorrell@centenary.usyd.edu.au
Telephone: +61-2-95656156 Fax: +61-2-95656101
Received: November 7, 2012
Revised: January 17, 2013
Accepted: February 2, 2013
Published online: May 21, 2013

AIM: To investigate the expression of dipeptidyl peptidase (DPP) 8 and DPP9 in lymphocytes and various models of liver fibrosis.

METHODS: DPP8 and DPP9 expression were measured in mouse splenic CD4+ T-cells, CD8+ T-cells and B-cells (B220+), human lymphoma cell lines and mouse splenocytes stimulated with pokeweed mitogen (PWM) or lipopolysaccharide (LPS), and in dithiothreitol (DTT) and mitomycin-C treated Raji cells. DPP8 and DPP9 expression were measured in epidermal growth factor (EGF) treated Huh7 hepatoma cells, in fibrotic liver samples from mice treated with carbon tetrachloride (CCl4) and from multidrug resistance gene 2 (Mdr2/Abcb4) gene knockout (gko) mice with biliary fibrosis, and in human end stage primary biliary cirrhosis (PBC).

RESULTS: All three lymphocyte subsets expressed DPP8 and DPP9 mRNA. DPP8 and DPP9 expression were upregulated in both PWM and LPS stimulated mouse splenocytes and in both Jurkat T- and Raji B-cell lines. DPP8 and DPP9 were downregulated in DTT treated and upregulated in mitomycin-C treated Raji cells. DPP9-transfected Raji cells exhibited more annexin V+ cells and associated apoptosis. DPP8 and DPP9 mRNA were upregulated in CCl4 induced fibrotic livers but not in the lymphocytes isolated from such livers, while DPP9 was upregulated in EGF stimulated Huh7 cells. In contrast, intrahepatic DPP8 and DPP9 mRNA expression levels were low in the Mdr2 gko mouse and in human PBC compared to non-diseased livers.

CONCLUSION: These expression patterns point to biological roles for DPP8 and DPP9 in lymphocyte activation and apoptosis and in hepatocytes during liver disease pathogenesis.

Keywords: Dipeptidyl peptidase, CD26, Lymphocytes, Liver fibrosis, Biliary fibrosis