PGE2 is known to suppress T cell proliferation and IL-2 production in many inflammatory conditions. Previous studies from our laboratory have shown that such suppression of T cell proliferation in burn and sepsis could result from alteration in T cell activation signaling molecule p59fyn. In this study, we examined the role of downstream signaling molecules NFAT and AP-1 in PGE2-mediated suppression of T cell in burn injury. These studies were carried out utilizing splenic T cells from sham and burn rats 3 days after injury. The data presented in this manuscript suggest a significant suppression of IL-2 production by T cells from burn injured rats compared with the T cells from sham rats. The suppression in T cell IL-2 production was accompanied by a decrease in the activation of NFAT and AP-1 as well as a decrease in T cell p59fyn kinase activity. The treatments of burn-injured animals with PGE2 synthesis blocker indomethacin prevented both the decrease in NFAT and AP-1 binding to IL-2 sequences. In vitro incubation of control rat T cells with PGE2 suppressed the activation of NFAT and AP-1. These results suggested that the suppression of T cell IL-2 production could result from PGE2-mediated alterations in the T cell signaling molecule p59fyn and NFAT/AP-1.

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