Inhibitory effect of a new anti-rheumatic drug T-614 on costimulatory molecule expression, cytokine production, and antigen presentation by synovial cells
A. Kawakami et al., Inhibitory effect of a new anti-rheumatic drug T-614 on costimulatory molecule expression, cytokine production, and antigen presentation by synovial cells, J LA CL MED, 133(6), 1999, pp. 566-574
Citations number
35
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
The present study wets undertaken to investigate the Immunoregulatory effec
ts of T-614 (3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-
4-one) on synovial cells in vitro. Synovial cells were cultured with T-614
in the presence or absence of various cytokines. After incubation, the cost
imulatory molecule expression on synovial cells and cytokine production in
culture supernatants were analyzed by an indirect immunofluorescence method
and enzyme-linked immunosorbent assay, respectively. We also examined the
effect of T-614 on the function of synovial cells as antigen-presenting cel
ls (APCs). The costimulatory molecules Including CD54, CD58, and CD106 were
constitutionally expressed on the surface of synovial cells. However, neit
her CD80 nor CD86 nor CD102 was found on the surface, and these costimulato
ry molecules could not be induced by any cytokines. T-614 itself did not af
fect the costimulatory molecule expression and cytokine production of unsti
mulated synovial cells. The stimulation of synovial cells with interferon-g
amma (IFN-gamma), interleukin-1 beta, or 12-O-tetradecanoyl phorbol 13-acet
ate enhanced the expression of costimulatory molecules and the proinflammat
ory cytokine production of these cells. Both the up-regulated expression of
these costimulatory molecules and the enhanced production of proinflammato
ry cytokines were significantly inhibited by T-614. Autologous T cell proli
feration in response to purified protein derivative by IFN-gamma-treated sy
novial cells was significantly suppressed by T-614. T-614 has considerable
immunosuppressive effects on synovial cells by inhibiting the costimulatory
molecule expression and cytokine production of these cells and the antigen
-specific T cell proliferation mediated by the synovial cells. These result
s suggest that T-614 plays an important immunoregulatory role in rheumatoid
synovial tissues.