{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:39:09Z","timestamp":1782974349378,"version":"3.54.5"},"reference-count":23,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:p> Acute lung injury (ALI) is mediated by an early proinflammatory response resulting from either a direct or indirect insult to the lung mediating neutrophil infiltration and consequent disruption of the alveolar capillary membrane ultimately leading to refractory hypoxemia. The mitogen-activated protein kinase (MAPK) pathways are a key component of the molecular response activated by those insults triggering the proinflammatory response in ALI. The MAPK pathways are counterbalanced by a set of dual-specific phosphatases (DUSP) that deactivate the kinases by removing phosphate groups from tyrosine or threonine residues. We have previously shown that one DUSP, MKP-2, regulates the MAPK pathway in a model of sepsis-induced inflammation; however, the role of MKP-2 in modulating the inflammatory response in ALI has not been previously investigated. We utilized both MKP-2-null (MKP-2<jats:sup>\u2212\/\u2212<\/jats:sup>) mice and MKP-2 knockdown in a murine macrophage cell line to elucidate the role of MKP-2 in regulating inflammation during ALI. Our data demonstrated attenuated proinflammatory cytokine production as well as decreased neutrophil infiltration in the lungs of MKP-2<jats:sup>\u2212\/\u2212<\/jats:sup> mice following direct, intratracheal LPS. Importantly, when challenged with a viable pathogen, this decrease in neutrophil infiltration did not impact the ability of MKP-2<jats:sup>\u2212\/\u2212<\/jats:sup> mice to clear either gram-positive or gram-negative bacteria. Furthermore, MKP-2 knockdown led to an attenuated proinflammatory response and was associated with an increase in phosphorylation of ERK and induction of a related DUSP, MKP-1. These data suggest that altering MKP-2 activity may have therapeutic potential to reduce lung inflammation in ALI without impacting pathogen clearance. <\/jats:p>","DOI":"10.1152\/ajplung.00063.2012","type":"journal-article","created":{"date-parts":[[2012,6,9]],"date-time":"2012-06-09T03:42:38Z","timestamp":1339213358000},"page":"L251-L258","source":"Crossref","is-referenced-by-count":26,"title":["Mitogen-activated protein kinase phosphatase 2, MKP-2, regulates early inflammation in acute lung injury"],"prefix":"10.1152","volume":"303","author":[{"given":"Timothy T.","family":"Cornell","sequence":"first","affiliation":[{"name":"Division of Pediatric Critical Care Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, C. S. Mott Children's Hospital, Ann Arbor, Michigan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Fleszar","sequence":"additional","affiliation":[{"name":"Division of Pediatric Critical Care Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, C. S. Mott Children's Hospital, Ann Arbor, Michigan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walker","family":"McHugh","sequence":"additional","affiliation":[{"name":"Division of Pediatric Critical Care Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, C. S. Mott Children's Hospital, Ann Arbor, Michigan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal B.","family":"Blatt","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, C. S. Mott Children's Hospital, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann Marie","family":"Le Vine","sequence":"additional","affiliation":[{"name":"Division of Pediatric Critical Care Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, C. S. Mott Children's Hospital, Ann Arbor, Michigan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Shanley","sequence":"additional","affiliation":[{"name":"Division of Pediatric Critical Care Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, C. S. 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