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A role of PP1/PP2A in mesenteric lymph node T cell suppression in a two-hit rodent model of alcohol intoxication and injury.
J Leukoc Biol. 2006 Mar; 79(3):453-62.JL

Abstract

This study examined the role of protein phosphatase type-1 (PP1), type-2A (PP2A), and mitogen-activated protein kinase phosphatase-1 (MKP-1) in altered mesenteric lymph node (MLN) T cell function in a two-hit model of alcohol (EtOH) intoxication and burn injury. Male rats (250 g) were gavaged with EtOH to achieve a blood EtOH level of approximately 100 mg/dL prior to burn or sham injury (25% total body surface area). MLN T cells harvested 24 h after injury show a significant decrease in p38 and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation in T cells from rats receiving a combined insult of EtOH intoxication and burn injury compared with rats receiving EtOH intoxication or burn injury alone. Treatment of cells with inhibitors of PP1/PP2A [calyculin A (CA) and okadaic acid (OA)] prevented the suppression in T cells p38 and ERK-1/2 activation. In addition, the suppression in interleukin-2 and interferon-gamma production was attenuated in T cells cultured in the presence of CA and OA. MKP-1 inhibitor triptolide did not prevent the suppression in T cells p38/ERK-1/2 and cytokine production. Furthermore, there was a significant decrease in PP1alpha phosphorylation (Thr320) and an increase in PP2A (Tyr307) phosphorylation in T cells following a combined insult of EtOH intoxication and burn injury. As phosphorylation of PP1 at Thr320 and PP2A at Tyr307 led to an inhibition of their enzymatic activities, the decrease in the PP1alpha phosphorylation correlates with an increase in its enzyme activity. Thus, these results suggest that activation of PP1 is likely to play a predominant role in T cell suppression following a combined insult of EtOH intoxication and burn injury.

Authors+Show Affiliations

Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Volker Hall G 094, 1670 University Boulevard, Birmingham, AL 35294, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16387841

Citation

Li, Xiaoling, et al. "A Role of PP1/PP2A in Mesenteric Lymph Node T Cell Suppression in a Two-hit Rodent Model of Alcohol Intoxication and Injury." Journal of Leukocyte Biology, vol. 79, no. 3, 2006, pp. 453-62.
Li X, Schwacha MG, Chaudry IH, et al. A role of PP1/PP2A in mesenteric lymph node T cell suppression in a two-hit rodent model of alcohol intoxication and injury. J Leukoc Biol. 2006;79(3):453-62.
Li, X., Schwacha, M. G., Chaudry, I. H., & Choudhry, M. A. (2006). A role of PP1/PP2A in mesenteric lymph node T cell suppression in a two-hit rodent model of alcohol intoxication and injury. Journal of Leukocyte Biology, 79(3), 453-62.
Li X, et al. A Role of PP1/PP2A in Mesenteric Lymph Node T Cell Suppression in a Two-hit Rodent Model of Alcohol Intoxication and Injury. J Leukoc Biol. 2006;79(3):453-62. PubMed PMID: 16387841.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A role of PP1/PP2A in mesenteric lymph node T cell suppression in a two-hit rodent model of alcohol intoxication and injury. AU - Li,Xiaoling, AU - Schwacha,Martin G, AU - Chaudry,Irshad H, AU - Choudhry,Mashkoor A, Y1 - 2005/12/30/ PY - 2006/1/3/pubmed PY - 2006/5/4/medline PY - 2006/1/3/entrez SP - 453 EP - 62 JF - Journal of leukocyte biology JO - J Leukoc Biol VL - 79 IS - 3 N2 - This study examined the role of protein phosphatase type-1 (PP1), type-2A (PP2A), and mitogen-activated protein kinase phosphatase-1 (MKP-1) in altered mesenteric lymph node (MLN) T cell function in a two-hit model of alcohol (EtOH) intoxication and burn injury. Male rats (250 g) were gavaged with EtOH to achieve a blood EtOH level of approximately 100 mg/dL prior to burn or sham injury (25% total body surface area). MLN T cells harvested 24 h after injury show a significant decrease in p38 and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation in T cells from rats receiving a combined insult of EtOH intoxication and burn injury compared with rats receiving EtOH intoxication or burn injury alone. Treatment of cells with inhibitors of PP1/PP2A [calyculin A (CA) and okadaic acid (OA)] prevented the suppression in T cells p38 and ERK-1/2 activation. In addition, the suppression in interleukin-2 and interferon-gamma production was attenuated in T cells cultured in the presence of CA and OA. MKP-1 inhibitor triptolide did not prevent the suppression in T cells p38/ERK-1/2 and cytokine production. Furthermore, there was a significant decrease in PP1alpha phosphorylation (Thr320) and an increase in PP2A (Tyr307) phosphorylation in T cells following a combined insult of EtOH intoxication and burn injury. As phosphorylation of PP1 at Thr320 and PP2A at Tyr307 led to an inhibition of their enzymatic activities, the decrease in the PP1alpha phosphorylation correlates with an increase in its enzyme activity. Thus, these results suggest that activation of PP1 is likely to play a predominant role in T cell suppression following a combined insult of EtOH intoxication and burn injury. SN - 0741-5400 UR - https://www.unboundmedicine.com/medline/citation/16387841/A_role_of_PP1/PP2A_in_mesenteric_lymph_node_T_cell_suppression_in_a_two_hit_rodent_model_of_alcohol_intoxication_and_injury_ L2 - https://doi.org/10.1189/jlb.0705369 DB - PRIME DP - Unbound Medicine ER -