{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:28:07Z","timestamp":1740137287134,"version":"3.37.3"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2005,12,30]],"date-time":"2005-12-30T00:00:00Z","timestamp":1135900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AA12901"],"award-info":[{"award-number":["AA12901"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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 \u223c100 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-\u03b3 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 PP1\u03b1 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 PP1\u03b1 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.<\/jats:p>","DOI":"10.1189\/jlb.0705369","type":"journal-article","created":{"date-parts":[[2005,12,31]],"date-time":"2005-12-31T01:24:24Z","timestamp":1135992264000},"page":"453-462","source":"Crossref","is-referenced-by-count":15,"title":["A role of PP1\/PP2A in mesenteric lymph node T cell suppression in a two-hit rodent model of alcohol intoxication and injury"],"prefix":"10.1093","volume":"79","author":[{"given":"Xiaoling","family":"Li","sequence":"first","affiliation":[{"name":"Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin G","family":"Schwacha","sequence":"additional","affiliation":[{"name":"Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irshad H","family":"Chaudry","sequence":"additional","affiliation":[{"name":"Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mashkoor A","family":"Choudhry","sequence":"additional","affiliation":[{"name":"Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,12,30]]},"reference":[{"key":"2023033022233159200_jlb0453-cit-b1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.alcohol.2004.05.004","article-title":"Impaired intestinal immunity and barrier function: a cause for enhanced bacterial translocation in alcohol intoxication and burn injury","volume":"33","author":"Choudhry","year":"2004","journal-title":"Alcohol"},{"key":"2023033022233159200_jlb0453-cit-b2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1089\/109629601750469456","article-title":"Ethanol abuse and the trauma patient","volume":"2","author":"Maier","year":"2001","journal-title":"Surg. Infect. (Larchmt)"},{"key":"2023033022233159200_jlb0453-cit-b3","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1097\/00005373-199506000-00019","article-title":"The impact of substance use on mortality and morbidity from thermal injury","volume":"38","author":"McGill","year":"1995","journal-title":"J. Trauma"},{"key":"2023033022233159200_jlb0453-cit-b4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/00004630-200021010-00016","article-title":"The epidemiology of fire-related deaths in Alabama, 1992\u20131997","volume":"21","author":"McGwin","year":"2000","journal-title":"J. Burn Care Rehabil."},{"key":"2023033022233159200_jlb0453-cit-b5","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0741-8329(02)00278-1","article-title":"Alcohol, injury, and cellular immunity","volume":"28","author":"Messingham","year":"2002","journal-title":"Alcohol"},{"key":"2023033022233159200_jlb0453-cit-b6","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/BF01546318","article-title":"Acute ethanol consumption synergizes with trauma to increase monocyte tumor necrosis factor \u03b1 production late postinjury","volume":"14","author":"Szabo","year":"1994","journal-title":"J. Clin. Immunol."},{"key":"2023033022233159200_jlb0453-cit-b7","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1093\/alcalc\/34.6.830","article-title":"Consequences of alcohol consumption on host defense","volume":"34","author":"Szabo","year":"1999","journal-title":"Alcohol Alcohol."},{"key":"2023033022233159200_jlb0453-cit-b8","first-page":"1927","article-title":"Alcohol abuse, alcoholism, and damage to the immune system\u2014a review","volume":"22","author":"Cook","year":"1998","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"2023033022233159200_jlb0453-cit-b9","doi-asserted-by":"crossref","first-page":"G937","DOI":"10.1152\/ajpgi.00235.2001","article-title":"Gut-associated lymphoid T cell suppression enhances bacterial translocation in alcohol and burn injury","volume":"282","author":"Choudhry","year":"2002","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"2023033022233159200_jlb0453-cit-b10","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.burns.2004.09.021","article-title":"Effect of acute alcohol ingestion prior to burn injury on intestinal bacterial growth and barrier function","volume":"31","author":"Kavanaugh","year":"2005","journal-title":"Burns"},{"key":"2023033022233159200_jlb0453-cit-b11","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/00005373-199502000-00008","article-title":"Chronic ethanol intake and burn injury: evidence for synergistic alteration in gut and immune integrity","volume":"38","author":"Napolitano","year":"1995","journal-title":"J. Trauma"},{"key":"2023033022233159200_jlb0453-cit-b12","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1097\/00024382-200116030-00003","article-title":"PGE2 suppresses intestinal T cell function in thermal injury: a cause of enhanced bacterial translocation","volume":"16","author":"Choudhry","year":"2001","journal-title":"Shock"},{"key":"2023033022233159200_jlb0453-cit-b13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1001\/archsurg.1986.01400010111015","article-title":"Thermal injury promotes bacterial translocation from the gastrointestinal tract in mice with impaired T-cell-mediated immunity","volume":"121","author":"Deitch","year":"1986","journal-title":"Arch. Surg."},{"key":"2023033022233159200_jlb0453-cit-b14","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1097\/00075198-200104000-00007","article-title":"Role of the gut lymphatic system in multiple organ failure","volume":"7","author":"Deitch","year":"2001","journal-title":"Curr. Opin. Crit. Care"},{"key":"2023033022233159200_jlb0453-cit-b15","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1097\/00003246-199302001-00010","article-title":"Bacterial translocation after thermal injury","volume":"21","author":"Herndon","year":"1993","journal-title":"Crit. Care Med."},{"key":"2023033022233159200_jlb0453-cit-b16","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1572-0241.1999.00797.x","article-title":"Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage","volume":"94","author":"Keshavarzian","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"2023033022233159200_jlb0453-cit-b17","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1046\/j.1365-2567.2002.01391.x","article-title":"T-cell antigen receptor signal transduction","volume":"105","author":"Cantrell","year":"2002","journal-title":"Immunology"},{"key":"2023033022233159200_jlb0453-cit-b18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1146\/annurev.immunol.20.091301.131133","article-title":"MAP kinases in the immune response","volume":"20","author":"Dong","year":"2002","journal-title":"Annu. Rev. Immunol."},{"key":"2023033022233159200_jlb0453-cit-b19","doi-asserted-by":"crossref","first-page":"28827","DOI":"10.1074\/jbc.R400012200","article-title":"T cell receptor signaling: beyond complex complexes","volume":"279","author":"Huang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2023033022233159200_jlb0453-cit-b20","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jss.2004.02.013","article-title":"Combined alcohol and burn injury differentially regulate P-38 and ERK activation in mesenteric lymph node T cell","volume":"121","author":"Choudhry","year":"2004","journal-title":"J. Surg. Res."},{"key":"2023033022233159200_jlb0453-cit-b21","doi-asserted-by":"crossref","first-page":"R37","DOI":"10.1152\/ajpregu.00782.2004","article-title":"Corticosterone suppresses mesenteric lymph node T cells by inhibiting p38\/ERK pathway and promotes bacterial translocation after alcohol and burn injury","volume":"289","author":"Li","year":"2005","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2023033022233159200_jlb0453-cit-b22","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S0955-0674(99)00075-7","article-title":"Protein phosphatases and the regulation of mitogen-activated protein kinase signaling","volume":"12","author":"Keyse","year":"2000","journal-title":"Curr. Opin. Cell Biol."},{"key":"2023033022233159200_jlb0453-cit-b23","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/00024382-200115030-00006","article-title":"TGF-\u03b2 abrogates TCR-mediated signaling by upregulating tyrosine phosphatases in T cells","volume":"15","author":"Choudhry","year":"2001","journal-title":"Shock"},{"key":"2023033022233159200_jlb0453-cit-b24","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.molimm.2004.04.015","article-title":"Protein tyrosine phosphatases in T cell physiology","volume":"41","author":"Mustelin","year":"2004","journal-title":"Mol. Immunol."},{"key":"2023033022233159200_jlb0453-cit-b25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0952-7915(97)80088-X","article-title":"Role of phosphatases in lymphocyte activation","volume":"9","author":"Neel","year":"1997","journal-title":"Curr. Opin. Immunol."},{"key":"2023033022233159200_jlb0453-cit-b26","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1042\/bj3110017","article-title":"Serine\/threonine protein phosphatases","volume":"311","author":"Wera","year":"1995","journal-title":"Biochem. J."},{"key":"2023033022233159200_jlb0453-cit-b27","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1006\/smim.2000.0219","article-title":"Extracellular signals and scores of phosphatases: all roads lead to MAP kinase","volume":"12","author":"Saxena","year":"2000","journal-title":"Semin. Immunol."},{"key":"2023033022233159200_jlb0453-cit-b28","doi-asserted-by":"crossref","first-page":"8101","DOI":"10.1074\/jbc.M411760200","article-title":"The role of mitogen-activated protein kinase phosphatase-1 in the response of alveolar macrophages to lipopolysaccharide: attenuation of proinflammatory cytokine biosynthesis via feedback control of p38","volume":"280","author":"Zhao","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2023033022233159200_jlb0453-cit-b29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1677\/joe.0.1780005","article-title":"MAP kinase phosphatase 1: a novel mediator of biological effects of glucocorticoids?","volume":"178","author":"Clark","year":"2003","journal-title":"J. Endocrinol."},{"key":"2023033022233159200_jlb0453-cit-b30","doi-asserted-by":"crossref","first-page":"7108","DOI":"10.1093\/emboj\/20.24.7108","article-title":"Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1","volume":"20","author":"Kassel","year":"2001","journal-title":"EMBO J."},{"key":"2023033022233159200_jlb0453-cit-b31","doi-asserted-by":"crossref","first-page":"54023","DOI":"10.1074\/jbc.M408444200","article-title":"The function of mitogen-activated protein kinase phosphatase-1 in peptidoglycan-stimulated macrophages","volume":"279","author":"Shepherd","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2023033022233159200_jlb0453-cit-b32","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4049\/jimmunol.174.1.456","article-title":"In vivo ethanol exposure down-regulates TLR2-, TLR4-, and TLR9-mediated macrophage inflammatory response by limiting p38 and ERK1\/2 activation","volume":"174","author":"Goral","year":"2005","journal-title":"J. Immunol."},{"key":"2023033022233159200_jlb0453-cit-b33","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/0968-0004(94)90127-9","article-title":"Inhibitors of protein kinases and phosphatases","volume":"19","author":"MacKintosh","year":"1994","journal-title":"Trends Biochem. Sci."},{"key":"2023033022233159200_jlb0453-cit-b34","doi-asserted-by":"crossref","first-page":"31917","DOI":"10.1074\/jbc.274.45.31917","article-title":"Distinct roles for PP1 and PP2A in phosphorylation of the retinoblastoma protein. PP2a regulates the activities of G(1) cyclin-dependent kinases","volume":"274","author":"Yan","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2023033022233159200_jlb0453-cit-b35","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0165-2478(90)90142-D","article-title":"Phosphatases PP1 and PP2A act after the G0\/G1 interface in lymphocyte activation","volume":"26","author":"Metcalfe","year":"1990","journal-title":"Immunol. Lett."},{"key":"2023033022233159200_jlb0453-cit-b36","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1006\/bbrc.1993.2566","article-title":"Okadaic acid inhibits glucocorticoid-induced apoptosis in T cell hybridomas at its late stage","volume":"197","author":"Ohoka","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023033022233159200_jlb0453-cit-b37","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1074\/jbc.M210196200","article-title":"Protein phosphatase 2A (PP2A) regulates interleukin-4-mediated STAT6 signaling","volume":"278","author":"Woetmann","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2023033022233159200_jlb0453-cit-b38","doi-asserted-by":"crossref","first-page":"6408","DOI":"10.4049\/jimmunol.169.11.6408","article-title":"Restraint of proinflammatory cytokine biosynthesis by mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages","volume":"169","author":"Chen","year":"2002","journal-title":"J. Immunol."},{"key":"2023033022233159200_jlb0453-cit-b39","doi-asserted-by":"crossref","first-page":"929","DOI":"10.4049\/jimmunol.160.2.929","article-title":"Prostaglandin E2 modulation of p59fyn tyrosine kinase in T lymphocytes during sepsis","volume":"160","author":"Choudhry","year":"1998","journal-title":"J. Immunol."},{"key":"2023033022233159200_jlb0453-cit-b40","doi-asserted-by":"crossref","first-page":"6238","DOI":"10.1074\/jbc.M409718200","article-title":"Protein phosphatase 2A regulates apoptosis in neutrophils by dephosphorylating both p38 MAPK and its substrate caspase 3","volume":"280","author":"Alvarado-Kristensson","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2023033022233159200_jlb0453-cit-b41","doi-asserted-by":"crossref","first-page":"6408","DOI":"10.1073\/pnas.91.14.6408","article-title":"Phosphorylation and inactivation of protein phosphatase 1 by cyclin- dependent kinases","volume":"91","author":"Dohadwala","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023033022233159200_jlb0453-cit-b42","doi-asserted-by":"crossref","first-page":"29470","DOI":"10.1074\/jbc.274.41.29470","article-title":"Inhibitory phosphorylation of PP1\u03b1 catalytic subunit during the G1\/S transition","volume":"274","author":"Liu","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2023033022233159200_jlb0453-cit-b43","doi-asserted-by":"crossref","first-page":"31091","DOI":"10.1074\/jbc.M503041200","article-title":"Protein phosphatase 2A regulates apoptosis in intestinal epithelial cells","volume":"280","author":"Ray","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2023033022233159200_jlb0453-cit-b44","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1189\/jlb.0503233","article-title":"Injury, sepsis, and the regulation of Toll-like receptor responses","volume":"75","author":"Murphy","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"2023033022233159200_jlb0453-cit-b45","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/jlb.63.1.51","article-title":"Thermal injury-induced immunosuppression in mice: the role of macrophage-derived reactive nitrogen intermediates","volume":"63","author":"Schwacha","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"2023033022233159200_jlb0453-cit-b46","first-page":"239","article-title":"The cellular basis of post-burn immunosuppression: macrophages and mediators","volume":"10","author":"Schwacha","year":"2002","journal-title":"Int. J. Mol. Med."},{"key":"2023033022233159200_jlb0453-cit-b47","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/00024382-199903000-00001","article-title":"The effects of injury on the adaptive immune response","volume":"11","author":"Lederer","year":"1999","journal-title":"Shock"},{"key":"2023033022233159200_jlb0453-cit-b48","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1046\/j.1432-1327.1999.00759.x","article-title":"Corticotropin increases protein tyrosine phosphatase activity by a cAMP-dependent mechanism in rat adrenal gland","volume":"265","author":"Paz","year":"1999","journal-title":"Eur. J. Biochem."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1189%2Fjlb.0705369","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/79\/3\/453\/49652655\/jlb0453.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/79\/3\/453\/49652655\/jlb0453.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:43:20Z","timestamp":1680223400000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/79\/3\/453\/6922818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12,30]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2005,12,30]]},"published-print":{"date-parts":[[2005,12,30]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.0705369","relation":{},"ISSN":["1938-3673","0741-5400"],"issn-type":[{"type":"electronic","value":"1938-3673"},{"type":"print","value":"0741-5400"}],"subject":[],"published-other":{"date-parts":[[2006,3]]},"published":{"date-parts":[[2005,12,30]]}}}