Inhibition of protein tyrosine phosphatases prevents mesenteric lymph node T-cell suppression following alcohol intoxication and burn injury.
کلید واژه ها
خلاصه
Previously, we have shown that acute alcohol (EtOH) intoxication before burn injury potentiates the suppression of mesenteric lymph node T-cell effector responses. Moreover, the suppression in T-cell was accompanied with a decrease in p-38 and extracellular-signal-regulated kinase (ERK) activation. This study examined the role of protein tyrosine phosphatases (PTP) in suppressed T-cell p-38, ERK, and cytokine production after EtOH intoxication and burn injury. A blood EtOH level of approximately 100 mg/dl in male rats (approximately 250 g) was achieved by gavaging animals with 5 ml of 20% EtOH suspension 4 hours before burn or sham injury (approximately 12.5% or 25% total body surface area [TBSA]). One day after injury, rats were killed and mesenteric lymph node T-cell cytokine (IL-2/IFN-gamma) production, p-38, and ERK activation were measured. As compared with shams, there was a significant decrease in T-cell cytokine production after 25% and not 12.5% TBSA burn injury. However, T-cell IL-2/IFN-gamma levels were significantly decreased in rats receiving a combined insult of EtOH and burn injury regardless of the percentage of burn area. Furthermore, we found a significant decrease in p-38 and ERK-1/2 phosphorylation in T-cells of rats receiving a combined insult of EtOH and 12.5% TBSA burn compared with shams. Treatment of cells with PTP inhibitor pervanadate (10 muM) prevented T-cell p-38/ERK suppression. The suppression in IL-2/IFN-gamma production was also attenuated in T-cells cultured in the presence of pervanadate. These findings suggest that an increase in PTP activity may contribute to T-cell suppression after EtOH intoxication and burn injury.