EXTRACELLULAR HUMAN T CELL LEUKEMIA VIRUS TYPE I TAX PROTEIN STIMULATES THE PROLIFERATION OF HUMAN SYNOVIAL CELLS

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Abstract

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 κB (NF-κB) DNA binding activity and the transcription of several NF-κB-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 α, 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-κB regulatory sequences.

Conclusion.

Our results suggest that extracellular Tax can regulate the expression of endogenous cellular genes in synovial cells and may contribute to the NF-κB-mediated synovial hyperplasia.

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