Transforming growth factor-beta increases the expression of aminopeptidase N/CD13 mRNA and protein in monocytes and monocytic cell lines.
Aminopeptidase N (APN)/CD13 is a membrane-bound surface ectopeptidase with a ubiquitous distribution. In hematopoiesis, APN/CD13 is expressed on stem cells and during most developmental stages of myeloid cells. Because APN/CD13 has been implicated in the trimming on the cell surface of peptides that protrude out of MHC class II molecules, we wanted to study the regulation of this membrane peptidase in antigen presenting cells by TGF-beta. TGF-beta is a potent inducer of the maturation of monocyte precursors towards a macrophage phenotype. Using competitive RT-PCR and cytofluorimetric analyses, we quantified the modulation of the APN/CD13 mRNA as well as protein expression by TGF-beta 1 and -2 and found a stimulation of the APN/CD13 expression in a time- and dose-dependent manner in monocytic cells. In U937 cells, the time course showed a maximum for APN/CD13 mRNA at 24 hours incubation with TGF-beta. In experiments with actinomycin D- treated cells was found a stabilization of APN/CD13 mRNA by TGF-beta 1. Contrary to the IL-4-induced expression of APN/CD13 as well as of MHC class II in monocytic cells, we could show that TGF-beta is able to augment the APN/CD13 expression but decreases the MHC class II expression.
Kehlen
A
A
Institute of Medical Immunology, Martin Luther University Halle, Germany. astrid.kehlen@medizin.uni-halle.de
Langner
J
J
Riemann
D
D
D018826:CD13 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010490:Pericardial Effusion / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051906:Smad7 Protein; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D020298:U937 Cells / Q000187:drug effects / Q000201:enzymology
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D009363:Neoplasm Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D018826:CD13 Antigens