Extracellular human T cell leukemia virus type I tax protein stimulates the proliferation of human synovial cells.
OBJECTIVE
The present study was designed to investigate whether the proliferation of normal synovial cells from patients with meniscus injury is stimulated by human T cell leukemia virus type I (HTLV-I) Tax protein.


METHODS
The effect of Tax protein on the proliferation of synovial cells was evaluated using a 3H-thymidine incorporation assay. Production of cytokines was determined by enzyme-linked immunosorbent assay. Nuclear factor kappaB (NF-kappaB) DNA binding activity and the transcription of several NF-kappaB-mediated genes was detected by electrophoretic mobility shift assay and reverse transcriptase-polymerase chain reaction.


RESULTS
The proliferation of synovial cells, as well as their expression of tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and interleukin-6, was significantly enhanced by extracellular Tax at concentrations of 2.5 pM to 25 nM. In contrast, extracellular bacterial extract did not change the cytokine expression or the proliferation of these cells. Proliferation of synovial cells induced by Tax protein may be due to activated expression of several cytokines and protooncogenes that contain NF-kappaB regulatory sequences.


CONCLUSIONS
Our results suggest that extracellular Tax can regulate the expression of endogenous cellular genes in synovial cells and may contribute to the NF-kappaB-mediated synovial hyperplasia.
Aono
H
H
St. Marianna University School of Medicine, Kawasaki, Japan.
Fujisawa
K
K
Hasunuma
T
T
Marriott
S J
SJ
Nishioka
K
K
D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005110:Extracellular Space / Q000276:immunology / Q000821:virology; D015870:Gene Expression / Q000276:immunology; D016356:Gene Products, tax / Q000235:genetics / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D015490:HTLV-I Infections / Q000276:immunology / Q000473:pathology*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D006965:Hyperplasia; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D015345:Oligonucleotide Probes; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D015533:Transcriptional Activation / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor