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Centro de Biología Molecular, "Severo Ochoa," Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain
Cyclooxygenase (COX), known to exist in two isoforms, COX-1 and
COX-2, is a key enzyme in prostaglandin synthesis and the target for
most nonsteroidal anti-inflammatory drugs. In this study, we show
that human T lymphocytes express the COX-2 isoenzyme. COX-2 mRNA and
protein were induced in both Jurkat and purified T cells stimulated by
TCR/CD3 or PMA activation. COX-2 mRNA was induced very early after
activation and superinduced by protein synthesis inhibitors, whereas it
was inhibited by the immunosuppressive drug cyclosporin A, identifying
it as an early T cell activation gene. Interestingly, treatment with
COX-2-specific inhibitors such as NS398 or Celecoxib severely
diminished early and late events of T cell activation, including CD25
and CD71 cell surface expression, IL-2, TNF-
, and IFN-
production
and cell proliferation, but not the expression of CD69, an immediate
early gene. COX-2 inhibitors also abolished induced transcription of
reporter genes driven by IL-2 and TNF- promoters. Moreover, induced
transcription from NF-
B- and NF-AT-dependent enhancers was also
inhibited. These results may have important implications in
anti-inflammatory therapy and open a new field on COX-2-selective
nonsteroidal anti-inflammatory drugs as modulators of the immune
activation.
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