PGE2 suppresses intestinal T cell function in thermal injury: a cause of enhanced bacterial translocation.
Increased gut bacterial translocation in burn and trauma patients has been demonstrated in a number of previous studies, however, the mechanism for such an increased gut bacterial translocation in injured patients remains poorly understood. Utilizing a rat model of burn injury, in the present study we examined the role of intestinal immune defense by analyzing the T cell functions. We investigated if intestinal T cells dysfunction contributes to bacterial translocation after burn injury. Also our study determined if burn-mediated alterations in intestinal T cell functions are related to enhanced release of PGE2. Finally, we examined whether or not burn-related alterations in intestinal T cell function are due to inappropriate activation of signaling molecule P59fyn, which is required for T cell activation and proliferation. The results presented here showed an increase in gut bacterial accumulation in mesenteric lymph nodes after thermal injury. This was accompanied by a decrease in the intestinal T cell proliferative responses. Furthermore, the treatments of burn-injured animals with PGE2 synthesis blocker (indomethacin or NS398) prevented both the decrease in intestinal T cell proliferation and enhanced bacterial translocation. Finally, our data suggested that the inhibition of intestinal T cell proliferation could result via PGE2-mediated down-regulation of the T cell activation-signaling molecule P59fyn. These findings support a role of T cell-mediated immune defense against bacterial translocation in burn injury.
Choudhry
M A
MA
Burn and Shock Trauma Institute, Department of Surgery and Physiology, Loyola University Chicago Medical Center Maywood, Illinois 60153, USA.
Fazal
N
N
Namak
S Y
SY
Haque
F
F
Ravindranath
T
T
Sayeed
M M
MM
D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects / Q000502:physiology*; D002056:Burns / Q000150:complications / Q000382:microbiology / Q000503:physiopathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007422:Intestines / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D008198:Lymph Nodes / Q000166:cytology / Q000382:microbiology; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D011518:Proto-Oncogene Proteins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D015232:Dinoprostone; D007213:Indomethacin