Inhibition of protein tyrosine phosphatases prevents mesenteric lymph node T-cell suppression following alcohol intoxication and burn injury

Xiaoling Li, Martin G. Schwacha, Irshad H. Chaudry, Mashkoor A. Choudhry

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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 ∼100 mg/dl in male rats (∼250 g) was achieved by gavaging animals with 5 ml of 20% EtOH suspension 4 hours before burn or sham injury (∼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-γ) 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-γ 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 μM) prevented T-cell p-38/ERK suppression. The suppression in IL-2/IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)519-530
Number of pages12
JournalJournal of Burn Care and Research
Volume29
Issue number3
DOIs
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Emergency Medicine
  • Rehabilitation

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