ERK and not p38 pathway is required for IL-12 restoration of T cell IL-2 and IFN-gamma in a rodent model of alcohol intoxication and burn injury.
Previous studies from our laboratory have shown that acute alcohol/ethanol (EtOH) intoxication combined with burn injury suppresses T cell IL-2 and IFN-gamma production by inhibiting p38 and ERK activation. Because IL-12 plays a major role in Th1 differentiation and IFN-gamma production, we examined whether diminished IL-2 and IFN-gamma production after EtOH plus burn injury resulted from a decrease in IL-12. Furthermore, we investigated whether IL-12 utilizes the p38/ERK pathway to modulate T cell IL-2 and IFN-gamma production after EtOH and burn injury. Male rats ( approximately 250 g) were gavaged with 5 ml of 20% EtOH 4 h before approximately 12.5% total body surface area burn or sham injury. Rats were sacrificed on day 1 after injury, and mesenteric lymph node T cells were isolated. T cells were stimulated with anti-CD3 in the absence or presence of rIL-12 (10 ng/ml) for 5 min and lysed. Lysates were analyzed for p38/ERK protein and phosphorylation levels using specific Abs and Western blot. In some experiments, T cells were cultured for 48 h with or without the inhibitors of p38 (10 microM SB203580/SB202190) or ERK (50 microM PD98059) to delineate the role of p38 and ERK in IL-12-mediated restoration of IL-2 and IFN-gamma. Our findings indicate that IL-12 normalizes both p38 and ERK activation in T cells, but the results obtained using p38 and ERK inhibitors indicate that the restoration of ERK plays a predominant role in IL-12-mediated restoration of T cell IL-2 and IFN-gamma production after EtOH and burn injury.
Li
Xiaoling
X
Department of Surgery, Burn and Shock Trauma Institute and Alcohol Research Program, Loyola University Chicago Medical Center, Maywood, IL 60153, USA.
Chaudry
Irshad H
IH
Choudhry
Mashkoor A
MA
D000435:Alcoholic Intoxication / Q000276:immunology*; D000818:Animals; D002056:Burns / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases