{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:42:42Z","timestamp":1776732162185,"version":"3.51.2"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>MAPKs are crucial for TNF-\u03b1 and IL-6 production by innate immune cells in response to TLR ligands. MAPK phosphatase 1 (Mkp-1) deactivates p38 and JNK, abrogating the inflammatory response. We have previously demonstrated that Mkp-1\u2212\/\u2212 mice exhibit exacerbated inflammatory cytokine production and increased mortality in response to challenge with LPS and heat-killed Staphylococcus aureus. However, the function of Mkp-1 in host defense during live Gram-negative bacterial infection remains unclear. We challenged Mkp-1+\/+ and Mkp-1\u2212\/\u2212 mice with live Escherichia coli i.v. to examine the effects of Mkp-1 deficiency on animal survival, bacterial clearance, metabolic activity, and cytokine production. We found that Mkp-1 deficiency predisposed animals to accelerated mortality and was associated with more robust production of TNF-\u03b1, IL-6 and IL-10, greater bacterial burden, altered cyclooxygenase-2 and iNOS expression, and substantial changes in the mobilization of energy stores. Likewise, knockout of Mkp-1 also sensitized mice to sepsis caused by cecal ligation and puncture. IL-10 inhibition by neutralizing Ab or genetic deletion alleviated increased bacterial burden. Treatment with the bactericidal antibiotic gentamicin, given 3 h after Escherichia coli infection, protected Mkp-1+\/+ mice from septic shock but had no effect on Mkp-1\u2212\/\u2212 mice. Thus, during Gram-negative bacterial sepsis Mkp-1 not only plays a critical role in the regulation of cytokine production but also orchestrates the bactericidal activities of the innate immune system and controls the metabolic response to stress.<\/jats:p>","DOI":"10.4049\/jimmunol.0804343","type":"journal-article","created":{"date-parts":[[2009,11,4]],"date-time":"2009-11-04T21:49:26Z","timestamp":1257371366000},"page":"7411-7419","source":"Crossref","is-referenced-by-count":88,"title":["Increased Inflammation, Impaired Bacterial Clearance, and Metabolic Disruption after Gram-Negative Sepsis in\n                    <i>Mkp-1<\/i>\n                    -Deficient Mice"],"prefix":"10.1093","volume":"183","author":[{"given":"W Joshua","family":"Frazier","sequence":"first","affiliation":[{"name":"Center for Perinatal Research, The Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43205"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyn M","family":"Wancket","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, The Ohio State University College of Veterinary Medicine , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang-An","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Kentucky Medical School , Lexington, KY 40536"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Meng","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif D","family":"Nelin","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43205"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C B","family":"Cato","sequence":"additional","affiliation":[{"name":"Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics , Karlsruhe,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusen","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43205"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine , Columbus, OH 43210"},{"name":"Department of Veterinary Biosciences, The Ohio State University College of Veterinary Medicine , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,1]]},"reference":[{"key":"2026012811255344000_R1","first-page":"1303","article-title":"Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.","volume-title":"Crit. 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