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M. FRESNO Y COLS. AN. R. ACAD. NAC. FARM

transcription factors such as nuclear factor (NF)-?B, NF-IL6 (C/EBP),
cAMP response element-binding protein (CREBP), Activator protein
(AP) -1, interferon regulatory factors (IRFs) and nuclear factor of
activated T cells (NFAT) (13-15) that induce COX-2 transcription in
different cell types. COX-2 transcripcional induction can be inhibited by
anti-inflammatory and immunosuppressive drugs as glucocorticoids and
Cyclosporin A (16, 17) as well as by anti-inflammatory cytokines such as
IL-4, IL-10 and IL-13 (18, 19).

FIGURE 1.- Biosynthesis of prostanoids. Arachidonic acid is liberated from the
membrane phospholipids by phospholipase A2 (PLA2) and converted to PGH2 and then
to PGG2 by cyclooxygenases (COX-1 or COX-2). Subsequent conversion of PGH2 to
different prostanoids (PGs, prostaglandins and TXs, thromboxanes) is catalyzed by the

respective synthases and isomerases. Prostanoids signal through G protein-coupled
receptors with seven trans-membrane domains. PGE2 signals via 4 different receptors

4