Role of NFAT and AP-1 in PGE2-mediated T cell suppression in burn injury.
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.
D000818:Animals; D002056:Burns / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011485:Protein Binding / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D015232:Dinoprostone; D007213:Indomethacin