IL-2-mediated upregulation of uPA and uPAR in natural killer cells.
Urokinase plasminogen activator (uPA) and its receptor uPAR play a major role in immune cell-mediated, including natural killer (NK) cell-mediated, degradation of extracellular matrices. Herein, we investigate the effects of IL-2 on NK cell uPA and uPAR. RNA and protein analyses showed upregulation of uPA and uPAR following IL-2 stimulation. Gel-shift assays and Western blots detected uPA and uPAR mRNA binding proteins (mRNABPs), previously shown to destabilize uPA and uPAR mRNA. Following IL-2 stimulation, a downregulation of uPAR mRNABP and a reciprocal induction of uPAR mRNA were noted. The increase in uPA following IL-2 stimulation appeared to be more transcriptionally regulated. These data suggest that IL-2 upregulates both uPA and uPAR in NK cells through posttranscriptional as well as transcriptional mechanisms, partially explaining increases in NK cell invasiveness following IL-2 stimulation.
Al-Atrash
Gheath
G
Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, USA.
Shetty
Sreerama
S
Idell
Steven
S
Xue
Yaming
Y
Kitson
Richard P
RP
Halady
Prathap Kumar Shetty
PK
Goldfarb
Ronald H
RH
D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000032:analysis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics*
D007376:Interleukin-2; C524898:PLAUR protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator