TY - JOUR
T1 - Regulation of tumor necrosis factor alpha promoter by human parvovirus B19 NS1 through activation of AP-1 and AP-2
AU - Fu, Yi
AU - Ishii, Keiko
AU - Munakata, Yasuhiko
AU - Saitoh, Takako
AU - Kaku, Mitsuo
AU - Sasaki, Takeshi
PY - 2002
Y1 - 2002
N2 - Human parvovirus B19 frequently causes acute and chronic arthritis in adults. The molecular mechanism of B19 arthritis, however, remains poorly understood. We previously showed that the transmission of B19 from rheumatoid synoviocytes to monocytic cells is associated with enhanced secretion of tumor necrosis factor alpha (TNF-α), which triggers inflammation, and interleukin-6. To determine the role of B19 in the production of TNF-α, we focused on the function of its nonstructural protein, NS1, and established monocytic U937 lines transduced with the NS1 gene under the control of an inducible promoter. Production of TNF-α mRNA and protein was elevated in a manner associated with NS1 expression. Reporter assays revealed that AP-1 and AP-2 motifs on the TNF-α promoter were responsible for NS1 -mediated up-regulation. Electrophoretic mobility shift assay showed specific binding of nuclear proteins from NS1 gene-transduced cells with the AP-1 or AP-2 probe. Antibodies against transcription factors AP-1 and AP-2 and anti-NS1 antibody inhibited the binding of nuclear proteins to the corresponding probes. These data indicate that NS1 up-regulates TNF-α transcription via activation of AP-1 and AP-2 in monocytic cells. The molecular mechanisms of NS1-mediated TNF-α expression would explain the pathogenesis of B19-associated inflammation.
AB - Human parvovirus B19 frequently causes acute and chronic arthritis in adults. The molecular mechanism of B19 arthritis, however, remains poorly understood. We previously showed that the transmission of B19 from rheumatoid synoviocytes to monocytic cells is associated with enhanced secretion of tumor necrosis factor alpha (TNF-α), which triggers inflammation, and interleukin-6. To determine the role of B19 in the production of TNF-α, we focused on the function of its nonstructural protein, NS1, and established monocytic U937 lines transduced with the NS1 gene under the control of an inducible promoter. Production of TNF-α mRNA and protein was elevated in a manner associated with NS1 expression. Reporter assays revealed that AP-1 and AP-2 motifs on the TNF-α promoter were responsible for NS1 -mediated up-regulation. Electrophoretic mobility shift assay showed specific binding of nuclear proteins from NS1 gene-transduced cells with the AP-1 or AP-2 probe. Antibodies against transcription factors AP-1 and AP-2 and anti-NS1 antibody inhibited the binding of nuclear proteins to the corresponding probes. These data indicate that NS1 up-regulates TNF-α transcription via activation of AP-1 and AP-2 in monocytic cells. The molecular mechanisms of NS1-mediated TNF-α expression would explain the pathogenesis of B19-associated inflammation.
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U2 - 10.1128/JVI.76.11.5395-5403.2002
DO - 10.1128/JVI.76.11.5395-5403.2002
M3 - Article
C2 - 11991968
AN - SCOPUS:0036095034
VL - 76
SP - 5395
EP - 5403
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 11
ER -