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 p roliferation of normal synovial cells from patients with meniscus inju ry is stimulated by human T cell leukemia virus type I (HTLV-I) Tax pr otein. Methods. The effect of Tax protein on the proliferation of syno vial cells was evaluated using a H-3-thymidine incorporation assay. Pr oduction of cytokines was determined by enzyme-linked immunosorbent as say. Nuclear factor kappa B (NF-kappa B) DNA binding activity and the transcription of several NF-kappa B-mediated genes was detected by ele ctrophoretic 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-macro phage 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 syno vial cells induced by Tax protein may be due to activated expression o f several cytokines and protooncogenes that contain NF-kappa B regulat ory sequences. Conclusion. Our results suggest that extracellular Tax can regulate the expression of endogenous cellular genes in synovial c ells and may contribute to the NF-kappa B-mediated synovial hyperplasi a.