Corticosterone suppresses mesenteric lymph node T cells by inhibiting p38/ERK pathway and promotes bacterial translocation after alcohol and burn injury.
Previous studies showed that alcohol (EtOH) intoxication before burn injury suppresses mesenteric lymph node (MLN) T cell functions and increases gut bacterial translocation. In this study, we examined whether corticosterone (Cort) plays any role in suppressing MLN T cell function and bacterial accumulation after EtOH intoxication and burn injury. Rats were gavaged with EtOH to achieve a blood EtOH level of approximately 100 mg/dl before receiving 25% total body surface area burn or sham injury. A group of rats was treated with the Cort synthesis inhibitor metyrapone (25 mg/kg) at the time of injury and on day 1 after injury. Two days after injury, a significant increase in blood Cort levels and suppression of MLN T cell proliferation and IL-2 production was observed in rats receiving combined insult of EtOH intoxication and burn injury compared with rats receiving EtOH intoxication or burn injury alone. There was no change in T cell apoptosis after combined insult of EtOH and burn injury. Furthermore, T cell suppression was accompanied by a significant decrease in p38 and ERK1/2 activation (phosphorylation). There was no difference in JNK activation after EtOH and burn injury. Treatment of rats with metyrapone prevented the suppression of MLN T cell proliferation, IL-2 production, and p38 and ERK1/2 phosphorylation. Restoration of T cell function in metyrapone-treated animals was also associated with the decrease in bacterial accumulation in MLN. These findings suggest that EtOH intoxication before burn injury augments Cort release, which suppresses MLN T cell function by inhibiting p38 and ERK1/2 activation and promotes bacterial accumulation in MLN after EtOH and burn injury.
Li
Xiaoling
X
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, VolkerHall G 094, 1670 Univ. Boulevard, Birmingham, AL 35294, USA.
Rana
Shadab N
SN
Kovacs
Elizabeth J
EJ
Gamelli
Richard L
RL
Chaudry
Irshad H
IH
Choudhry
Mashkoor A
MA
D000435:Alcoholic Intoxication / Q000150:complications*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis; D018988:Bacterial Translocation; D002056:Burns / Q000150:complications* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008643:Mesentery; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000906:Antibodies; D017252:CD3 Complex; D007376:Interleukin-2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003345:Corticosterone