Transcriptional regulation of cytosol and membrane alanyl-aminopeptidase in human T cell subsets.
Aminopeptidase inhibitors strongly affect the proliferation and function of immune cells in man and animals and are promising agents for the pharmacological treatment of inflammatory or autoimmune diseases. Membrane alanyl-aminopeptidase (mAAP) has been considered as the major target of these anti-inflammatory aminopeptidase inhibitors. Recent evidence also points to a role of the cytosol alanyl-aminopeptidase (cAAP) in the immune response. In this study we used quantitative RT-PCR to determine the mRNA expression of both cAAP and mAAP in resting and activated peripheral T cells and also in CD4+, CD8+, Th1, Th2 and Treg (CD4+ CD25+) subpopulations. Both mAAP and cAAP mRNAs were expressed in all cell types investigated, and in response to activation their expression appeared to be upregulated in CD8+ cells, but downregulated in Treg cells. In CD4+ cells, mAAP and cAAP mRNAs were affected in opposite ways in response to activation. The cAAP-specific inhibitor, PAQ-22, did not affect either cAAP or mAAP expression in activated CD4+ or CD8+ cells, whereas in activated Treg cells it markedly upregulated the mRNA levels of both aminopeptidases. The non-discriminatory inhibitor, phebestin, significantly increased the amount of mAAP and cAAP mRNA in CD4+ and that of cAAP in Treg cells.
Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
Alicja
A
Bukowska
Janine
J
Tadje
Marco
M
Arndt
Carmen
C
Wolke
Thilo
T
Kähne
Jaqueline
J
Bartsch
Jürgen
J
Faust
Klaus
K
Neubert
Yuichi
Y
Hashimoto
Uwe
U
Lendeckel
D000410:Alanine Transaminase / Q000037:antagonists & inhibitors / Q000235:genetics*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000201:enzymology*; D018417:Th1 Cells / Q000201:enzymology; D018418:Th2 Cells / Q000201:enzymology
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D012333:RNA, Messenger; C104995:phebestin; D000410:Alanine Transaminase; D000626:Aminopeptidases