Abstract
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:
Biliary fibrosis; CD26; Dipeptidyl peptidase; Liver fibrosis; Lymphocytes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / deficiency
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ATP Binding Cassette Transporter, Subfamily B / genetics
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ATP-Binding Cassette Sub-Family B Member 4
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Adult
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Aged
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Animals
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Apoptosis
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Carbon Tetrachloride
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Chemical and Drug Induced Liver Injury / enzymology*
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Chemical and Drug Induced Liver Injury / etiology
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Chemical and Drug Induced Liver Injury / genetics
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Chemical and Drug Induced Liver Injury / immunology
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Chemical and Drug Induced Liver Injury / pathology
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Dipeptidases / genetics
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Dipeptidases / metabolism*
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Dipeptidyl Peptidase 4 / deficiency
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Dipeptidyl Peptidase 4 / genetics
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / genetics
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism*
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Endopeptidases
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Female
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Gelatinases / deficiency
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Gelatinases / genetics
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Humans
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Jurkat Cells
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Liver / enzymology*
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Liver / innervation
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Liver / pathology
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Liver Cirrhosis, Biliary / enzymology*
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Liver Cirrhosis, Biliary / etiology
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Liver Cirrhosis, Biliary / genetics
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Liver Cirrhosis, Biliary / immunology
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Liver Cirrhosis, Biliary / pathology
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Liver Cirrhosis, Experimental / enzymology*
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Liver Cirrhosis, Experimental / etiology
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Liver Cirrhosis, Experimental / genetics
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Liver Cirrhosis, Experimental / immunology
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Liver Cirrhosis, Experimental / pathology
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Lymphocyte Activation*
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Lymphocyte Subsets / enzymology*
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Lymphocyte Subsets / immunology
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Male
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Membrane Proteins / deficiency
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Membrane Proteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Middle Aged
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RNA, Messenger / metabolism
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Serine Endopeptidases / deficiency
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Serine Endopeptidases / genetics
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Time Factors
Substances
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ATP Binding Cassette Transporter, Subfamily B
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Membrane Proteins
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RNA, Messenger
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Carbon Tetrachloride
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Endopeptidases
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Dipeptidases
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DPP9 protein, human
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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DPP8 protein, human
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Dipeptidyl Peptidase 4
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Dpp4 protein, mouse
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dipeptidyl peptidase 8, mouse
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dipeptidyl peptidase 9, mouse
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Serine Endopeptidases
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fibroblast activation protein alpha
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Gelatinases