{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:24:27Z","timestamp":1793042667057,"version":"4.5.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2008,4,1]],"date-time":"2008-04-01T00:00:00Z","timestamp":1207008000000},"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":[[2008,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The activation of p38\u03b1, a MAPK family member, is associated with macrophage activation by microbial pattern molecules, such as LPS. The requirement of p38\u03b1 in inflammatory responses has been shown in a number of studies using chemical inhibitors, though the inhibitors also inhibit p38\u03b2 and perhaps some other enzymes. In this study, we used conditional knockout of p38\u03b1 in macrophages to address the role of p38\u03b1 in macrophage activation. We found that p38\u03b1 deficiency causes a significant inhibition in the production of LPS-induced TNF-\u03b1, IL-12, and IL-18, but it has little or no effect on IL-6 or IFN-\u03b2 production. Knockout of p38\u03b1 in macrophages did not affect LPS-induced activation of the other major signaling pathways (NF-\u03baB, Jnk, and Erk), nor did it affect the transcriptional activity of NF-\u03baB. It had little inhibitory effect on LPS-induced AP-1 activity, but it significantly inhibited LPS-induced C\/EBP-\u03b2 and CREB activation, indicating that the role of p38\u03b1 in cytokine production in macrophages is at least in part through its regulation of C\/EBP-\u03b2 and CREB activation. In addition, we also confirmed that p38\u03b1 is important for phagocytosis of bacteria by macrophages. Our in vivo studies with two murine models showed that p38\u03b1 is involved in sepsis. Collectively, our data demonstrate that p38\u03b1 is an important player in inflammatory responses.<\/jats:p>","DOI":"10.4049\/jimmunol.180.7.5075","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:12:56Z","timestamp":1397862776000},"page":"5075-5082","source":"Crossref","is-referenced-by-count":140,"title":["Macrophage Deletion of p38\u03b1 Partially Impairs Lipopolysaccharide-Induced Cellular Activation"],"prefix":"10.1093","volume":"180","author":[{"given":"Young Jun","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyuki","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Mols","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxun","family":"Ren","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute and the Departments of Anesthesiology and Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinbin","family":"Wang","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute and the Departments of Anesthesiology and Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahuai","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,4,1]]},"reference":[{"key":"2025033118422891200_R1","first-page":"499","volume-title":"Nat. Rev. Immunol.","year":"2004"},{"key":"2025033118422891200_R2","first-page":"447","volume-title":"Trends Immunol.","year":"2005"},{"key":"2025033118422891200_R3","first-page":"257","volume-title":"Nature","year":"2004"},{"key":"2025033118422891200_R4","first-page":"1198","volume-title":"Nat. Immunol.","year":"2005"},{"key":"2025033118422891200_R5","first-page":"169","volume-title":"Nat. Rev. Immunol.","year":"2003"},{"key":"2025033118422891200_R6","first-page":"808","volume-title":"Science","year":"1994"},{"key":"2025033118422891200_R7","first-page":"25009","volume-title":"J. Biol. Chem.","year":"1993"},{"key":"2025033118422891200_R8","first-page":"739","volume-title":"Nature","year":"1994"},{"key":"2025033118422891200_R9","first-page":"1","volume-title":"Cell Signal.","year":"2000"},{"key":"2025033118422891200_R10","first-page":"1358","volume-title":"Biochim. Biophys. Acta","year":"2007"},{"key":"2025033118422891200_R11","first-page":"433","volume-title":"Pharmacol. Res.","year":"2004"},{"key":"2025033118422891200_R12","first-page":"6349","volume-title":"J. Immunol.","year":"2000"},{"key":"2025033118422891200_R13","first-page":"433","volume-title":"Mol. Pharmacol.","year":"1995"},{"key":"2025033118422891200_R14","first-page":"5367","volume-title":"J. Immunol.","year":"1999"},{"key":"2025033118422891200_R15","first-page":"12901","volume-title":"J. Biol. Chem.","year":"1998"},{"key":"2025033118422891200_R16","first-page":"467","volume-title":"J. Immunol.","year":"1998"},{"key":"2025033118422891200_R17","first-page":"28373","volume-title":"J. Biol. Chem.","year":"1997"},{"key":"2025033118422891200_R18","first-page":"44","volume-title":"Biochem. Biophys. Res. Commun.","year":"1997"},{"key":"2025033118422891200_R19","first-page":"1453","volume-title":"J. Pharmacol. Exp. Ther.","year":"1996"},{"key":"2025033118422891200_R20","first-page":"109","volume-title":"Mol. Cell","year":"2000"},{"key":"2025033118422891200_R21","first-page":"859","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2025033118422891200_R22","first-page":"10454","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2000"},{"key":"2025033118422891200_R23","first-page":"221","volume-title":"Cell","year":"2000"},{"key":"2025033118422891200_R24","first-page":"741","volume-title":"Nat. Genet.","year":"2007"},{"key":"2025033118422891200_R25","first-page":"750","volume-title":"Nat. Genet.","year":"2007"},{"key":"2025033118422891200_R26","first-page":"1245","volume-title":"EMBO J.","year":"2007"},{"key":"2025033118422891200_R27","first-page":"1175","volume-title":"Genes Dev.","year":"2005"},{"key":"2025033118422891200_R28","first-page":"1218","volume-title":"J. Biol. Chem.","year":"1996"},{"key":"2025033118422891200_R29","first-page":"1441","volume-title":"J. Exp. Med.","year":"2003"},{"key":"2025033118422891200_R30","first-page":"463","volume-title":"Cell","year":"1998"},{"key":"2025033118422891200_R31","first-page":"52","volume-title":"Shock","year":"2005"},{"key":"2025033118422891200_R32","first-page":"1434","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1996"},{"key":"2025033118422891200_R33","first-page":"265","volume-title":"Transgenic Res.","year":"1999"},{"key":"2025033118422891200_R34","first-page":"44","volume-title":"FEBS Lett.","year":"2000"},{"key":"2025033118422891200_R35","first-page":"4831","volume-title":"EMBO J.","year":"2002"},{"key":"2025033118422891200_R36","first-page":"94","volume-title":"Nat. Cell Biol.","year":"1999"},{"key":"2025033118422891200_R37","first-page":"552","volume-title":"Nature","year":"1985"},{"key":"2025033118422891200_R38","first-page":"1014","volume-title":"Science","year":"2004"},{"key":"2025033118422891200_R39","first-page":"46961","volume-title":"J. Biol. Chem.","year":"2003"},{"key":"2025033118422891200_R40","first-page":"421","volume-title":"Mol. Cell","year":"2001"},{"key":"2025033118422891200_R41","first-page":"2180","volume-title":"J. Med. Chem.","year":"1999"},{"key":"2025033118422891200_R42","first-page":"15434","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2003"},{"key":"2025033118422891200_R43","first-page":"4178","volume-title":"J. Immunol.","year":"2005"},{"key":"2025033118422891200_R44","first-page":"1897","volume-title":"EMBO J.","year":"1990"},{"key":"2025033118422891200_R45","first-page":"1171","volume-title":"Cytokine","year":"2000"},{"key":"2025033118422891200_R46","first-page":"6084","volume-title":"Mol. Cell Biol.","year":"2000"},{"key":"2025033118422891200_R47","first-page":"514","volume-title":"Infect. Immun.","year":"2005"},{"key":"2025033118422891200_R48","first-page":"4572","volume-title":"Mol. Cell Biol.","year":"1997"},{"key":"2025033118422891200_R49","first-page":"2608","volume-title":"J. Immunol.","year":"2001"},{"key":"2025033118422891200_R50","first-page":"3966","volume-title":"Infect. Immun.","year":"1995"},{"key":"2025033118422891200_R51","first-page":"298","volume-title":"J. Immunol.","year":"1997"},{"key":"2025033118422891200_R52","first-page":"1005","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2025033118422891200_R53","first-page":"143","volume-title":"J. Immunol.","year":"1999"},{"key":"2025033118422891200_R54","first-page":"6156","volume-title":"J. Immunol.","year":"1997"},{"key":"2025033118422891200_R55","first-page":"2000","volume-title":"J. Immunol.","year":"1999"},{"key":"2025033118422891200_R56","first-page":"3198","volume-title":"J. Immunol.","year":"2000"},{"key":"2025033118422891200_R57","first-page":"566","volume-title":"J. Cell Biochem.","year":"2005"},{"key":"2025033118422891200_R58","first-page":"703","volume-title":"Blood","year":"2003"},{"key":"2025033118422891200_R59","first-page":"23814","volume-title":"J. Biol. Chem.","year":"2000"},{"key":"2025033118422891200_R60","first-page":"45","volume-title":"Bone","year":"2001"},{"key":"2025033118422891200_R61","first-page":"3635","volume-title":"J. Immunol.","year":"2006"},{"key":"2025033118422891200_R62","first-page":"51150","volume-title":"J. Biol. Chem.","year":"2003"},{"key":"2025033118422891200_R63","first-page":"2871","volume-title":"Mol. Cell Biol.","year":"2003"},{"key":"2025033118422891200_R64","first-page":"239","volume-title":"Cell","year":"2000"},{"key":"2025033118422891200_R65","first-page":"36993","volume-title":"J. Biol. Chem.","year":"2003"},{"key":"2025033118422891200_R66","first-page":"C399","volume-title":"Am. J. Physiol.","year":"2003"},{"key":"2025033118422891200_R67","first-page":"15319","volume-title":"J. Biol. Chem.","year":"2007"},{"key":"2025033118422891200_R68","first-page":"81","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2025033118422891200_R69","first-page":"1953","volume-title":"Infect. Immun.","year":"2000"},{"key":"2025033118422891200_R70","first-page":"147","volume-title":"J. Exp. Med.","year":"2000"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/180\/7\/5075\/62819385\/zim00708005075.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/180\/7\/5075\/62819385\/zim00708005075.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T21:56:48Z","timestamp":1743458208000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/180\/7\/5075\/8021607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,4,1]]},"references-count":70,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2008,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.180.7.5075","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2008,4]]},"published":{"date-parts":[[2008,4,1]]}}}