title: Regulation of dipeptidyl peptidase 8 and 9 expression in activated lymphocytes and injured liver.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These expression patterns point to biological roles for DPP8 and DPP9 in lymphocyte activation and apoptosis and in hepatocytes during liver disease pathogenesis.
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Sumaiya
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Chen
authors.forename: Tsun-Wen
authors.initials: TW
authors.lastname: Yao
authors.forename: Katerina
authors.initials: K
authors.lastname: Ajami
authors.forename: Xin M
authors.initials: XM
authors.lastname: Wang
authors.forename: Yury
authors.initials: Y
authors.lastname: Popov
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Patrick
authors.initials: P
authors.lastname: Bertolino
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.forename: Denise Mt
authors.initials: DM
authors.lastname: Yu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Gorrell
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000172:deficiency / Q000235:genetics; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004150:Dipeptidases / Q000235:genetics / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000172:deficiency / Q000235:genetics; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000172:deficiency / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008099:Liver / Q000201:enzymology* / Q000294:innervation / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D000097202:ATP-Binding Cassette Sub-Family B Member 4; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D002251:Carbon Tetrachloride; D004150:Dipeptidases; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D000097202:ATP-Binding Cassette Sub-Family B Member 4; D000099167:Fibroblast Activation Protein Alpha; C471241:DPP9 protein, human; C487997:DPP8 protein, human; C545245:Dpp4 protein, mouse; C585325:dipeptidyl peptidase 8, mouse; C585326:dipeptidyl peptidase 9, mouse
keywords: Biliary fibrosis; CD26; Dipeptidyl peptidase; Liver fibrosis; Lymphocytes