Prostaglandin E2 modulation of p59fyn tyrosine kinase in T lymphocytes during sepsis

Prostaglandin E-2 (PGE(2)) has been implicated in the suppression of T cell IL-2 production and proliferation during burn and sepsis. The present study evaluated the potential intracellular mechanism of suppressed T cell responses by assessing the activation of p59(fyn) kinase in T cells from septic rats as well as the T cells incubated with PCE2. p59(fyn) is known to regulate T cell functions. Sepsis was induced in rats by implanting fecal pellets containing Escherichia coli (150 CFU) and Bacteroides fragilis (10(4) CFU) into the abdominal cavity. For the assessment of PGE(2) role in sepsis, a group of septic rats were treated with indomethacin, which inhibits endogenous PGE(2) synthesis. As assessed by immunoblotting or in vitro kinase assay, a more than 40% inhibition of p59(fyn) phosphorylation and kinase activity was observed in septic rat T cells compared with the T cells from sterile or control rats. A similar inhibition in p59(fyn) phosphorylation and kinase activity was observed in PGE(2)-treated T cells compared with the T cells incubated in the absence of PGE(2). The septic-related suppression in p59(fyn) phosphorylation and kinase activity in T cells was prevented in rats treated with indomethacin. We observed that the inhibition in p59(fyn) activation in septic or PGE(2)-treated T cells was due primarily to a suppression in p59(fyn) phosphorylation and not due to alterations in p59(fyn) protein expression. These findings suggest that PCE2 released during sepsis could contribute to the sepsis-related suppression in T cell proliferation by attenuating p59(fyn) phosphorylation and its kinase activity.