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Role of p38/ERK Pathway in IL‐12 Restoration of T Cell IL‐2/IFN‐γ Production Following Alcohol (EtOH) Intoxication and Injury
Author(s) -
Li Xiaoling,
Schwacha Martin G,
Chaudry Irshad H,
Choudhry Mashkoor A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.852.14
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , burn injury , t cell , chemistry , cell , medicine , immunology , microbiology and biotechnology , kinase , biology , immune system , biochemistry , surgery
The mechanism by which EtOH potentiates post burn pathogenesis remains unknown. We have shown that EtOH intoxication prior to burn injury potentiates the suppression of mesenteric lymph node (MLN) T cell IL‐2/IFN‐γ and enhances bacterial translocation. The suppression in T cell was accompanied with a decrease in p38 and ERK activation. Since we also found a decrease in IL‐12, this study examined whether IL‐12 restitution restores T cell IL‐2/IFN‐γ following EtOH and burn injury and whether p38/ERK pathway is involved in IL‐12 restoration of IL‐2/IFN‐γ. Male rats (250g) were gavaged with 5 ml of 20% EtOH 4h prior to ~12.5% total body surface area burn or sham injury. Rats were sacrificed on day one after injury. MLN T cells were isolated, stimulated with anti‐CD3 in the absence or presence of recombinant (r) IL‐12 (10ng/ml) for 5 min and lysed for p38 and ERK1/2 measurements. In some experiments, T cells were cultured for 48h with or without the inhibitors of p38 (10μM SB203580) or ERK (50μM PD98059). Results indicate that the incubation of T cells with rIL‐12 prevents the suppression of T cell IL‐2/IFN‐γ following EtOH and burn injury. Furthermore, IL‐12 normalizes both p38 and ERK activation in T cells, but results obtained using p38 and ERK inhibitors indicate that the restoration of ERK and not p38 is critical to IL‐12‐mediated restoration of T cell IL‐2/IFN‐γ production following EtOH and burn injury. (R01AA015731–01A2)