Prostaglandin E2 modulation of p59fyn tyrosine kinase in T lymphocytes during sepsis.
Prostaglandin E2 (PGE2) 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 p59fyn kinase in T cells from septic rats as well as the T cells incubated with PGE2. p59fyn 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 PGE2 role in sepsis, a group of septic rats were treated with indomethacin, which inhibits endogenous PGE2 synthesis. As assessed by immunoblotting or in vitro kinase assay, a more than 40% inhibition of p59fyn 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 p59fyn phosphorylation and kinase activity was observed in PGE2-treated T cells compared with the T cells incubated in the absence of PGE2. The septic-related suppression in p59fyn phosphorylation and kinase activity in T cells was prevented in rats treated with indomethacin. We observed that the inhibition in p59fyn activation in septic or PGE2-treated T cells was due primarily to a suppression in p59fyn phosphorylation and not due to alterations in p59fyn protein expression. These findings suggest that PGE2 released during sepsis could contribute to the sepsis-related suppression in T cell proliferation by attenuating p59fyn phosphorylation and its kinase activity.
Choudhry
M A
MA
Department of Physiology, Burn and Shock Trauma Institute, Loyola University Chicago Medical Center, Maywood, IL 60153, USA.
Uddin
S
S
Sayeed
M M
MM
D000818:Animals; D001442:Bacteroides Infections / Q000201:enzymology / Q000276:immunology; D001441:Bacteroides fragilis / Q000276:immunology; D015232:Dinoprostone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D004927:Escherichia coli Infections / Q000201:enzymology / Q000276:immunology; D007213:Indomethacin / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000201:enzymology* / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D015232:Dinoprostone; D007213:Indomethacin