Human immunodeficiency virus-1-tat induces matrix metalloproteinase-9 in monocytes through protein tyrosine phosphatase-mediated activation of nuclear transcription factor NF-kappaB.
We have previously shown that human immunodeficiency virus (HIV)-1-tat induces the production of matrix metalloproteinase-9 (MMP-9) in human monocytes by a mechanism that is not understood. In the present report, we demonstrate that HIV-tat-induced expression of MMP-9 is blocked by inhibitors of protein tyrosine phosphatases (PTPases). PTPase inhibitors also blocked HIV-tat-induced nuclear transcription factor NF-kappaB activation and IkappaBalpha degradation required for MMP-9 induction. These results suggest that HIV-tat induces MMP-9 in human monocytes through activation of PTPase and NF-kappaB.
Kumar
A
A
Cytokine Research Section, Department of Molecular Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe St. Box 143, Houston, TX 77030, USA.
Dhawan
S
S
Mukhopadhyay
A
A
Aggarwal
B B
BB
D004268:DNA-Binding Proteins / Q000378:metabolism; D004790:Enzyme Induction; D015696:Gene Products, tat / Q000494:pharmacology*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009000:Monocytes / Q000201:enzymology / Q000821:virology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020298:U937 Cells; D054322:tat Gene Products, Human Immunodeficiency Virus
D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D054322:tat Gene Products, Human Immunodeficiency Virus; D000072000:NF-KappaB Inhibitor alpha; D017027:Protein Tyrosine Phosphatases; D020780:Matrix Metalloproteinase 9