{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:45:09Z","timestamp":1780051509754,"version":"3.53.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2005,3,1]],"date-time":"2005-03-01T00:00:00Z","timestamp":1109635200000},"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":[[2005,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The p38 mitogen-activated protein kinase (MAPK) plays a critical role in the activation of inflammatory cells. Therefore, we investigated the antiinflammatory effects of a respirable p38\u03b1 MAPK antisense oligonucleotide (p38\u03b1-ASO) in a mouse asthma model. A potent and selective p38\u03b1-ASO was characterized in vitro. Inhalation of aerosolized p38\u03b1-ASO using an aerosol chamber dosing system produced measurable lung deposition of ASO and significant reduction of ovalbumin (OVA-)-induced increases in total cells, eosinophils, and interleukin 4 (IL-4), IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and dose-dependent inhibition of airway hyperresponsiveness in allergen-challenged mice. Furthermore, inhaled p38\u03b1-ASO markedly inhibited OVA-induced lung tissue eosinophilia and airway mucus hypersecretion. Quantitative polymerase chain reaction analysis of bronchoalveolar lavage fluid cells and peribronchial lymph node cells showed that p38\u03b1-ASO significantly reduced p38\u03b1 MAPK mRNA expression. Nose-only aerosol exposure of mice verified the p38\u03b1-ASO\u2013induced inhibition of OVA-induced pulmonary eosinophilia, mucus hypersecretion, and airway hyperresponsiveness. None of the effects of the p38\u03b1-ASO were produced by a six-base mismatched control oligonucleotide. These findings demonstrate antisense pharmacodynamic activity in the airways after aerosol delivery and suggest that a p38\u03b1 MAPK ASO approach may have therapeutic potential for asthma and other inflammatory lung diseases.<\/jats:p>","DOI":"10.1164\/rccm.200408-1006oc","type":"journal-article","created":{"date-parts":[[2004,11,19]],"date-time":"2004-11-19T20:24:38Z","timestamp":1100895878000},"page":"571-578","source":"Crossref","is-referenced-by-count":139,"title":["Inhaled p38\u03b1 Mitogen-activated Protein Kinase Antisense Oligonucleotide Attenuates Asthma in Mice"],"prefix":"10.1093","volume":"171","author":[{"given":"Wei","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Pharmacology, National University of Singapore; Department of Rheumatology, Allergy, and Immunology, Tan Tock Seng Hospital, Singapore; Department of Antisense Drug Discovery, ISIS Pharmaceuticals, Carlsbad, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine H. P.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National University of Singapore; Department of Rheumatology, Allergy, and Immunology, Tan Tock Seng Hospital, Singapore; Department of Antisense Drug Discovery, ISIS Pharmaceuticals, Carlsbad, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National University of Singapore; Department of Rheumatology, Allergy, and Immunology, Tan Tock Seng Hospital, Singapore; Department of Antisense Drug Discovery, ISIS Pharmaceuticals, Carlsbad, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Crosby","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National University of Singapore; Department of Rheumatology, Allergy, and Immunology, Tan Tock Seng Hospital, Singapore; Department of Antisense Drug Discovery, ISIS Pharmaceuticals, Carlsbad, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Hwa","family":"Choo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National University of Singapore; Department of Rheumatology, Allergy, and Immunology, Tan Tock Seng Hospital, Singapore; Department of Antisense Drug Discovery, ISIS Pharmaceuticals, Carlsbad, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard P.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National University of Singapore; Department of Rheumatology, Allergy, and Immunology, Tan Tock Seng Hospital, Singapore; Department of Antisense Drug Discovery, ISIS Pharmaceuticals, Carlsbad, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Karras","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National University of Singapore; Department of Rheumatology, Allergy, and Immunology, Tan Tock Seng Hospital, Singapore; Department of Antisense Drug Discovery, ISIS Pharmaceuticals, Carlsbad, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. S. Fred","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National University of Singapore; Department of Rheumatology, Allergy, and Immunology, Tan Tock Seng Hospital, Singapore; Department of Antisense Drug Discovery, ISIS Pharmaceuticals, Carlsbad, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,3,15]]},"reference":[{"key":"2026032606192029100_BIB1","first-page":"5","volume-title":"Respir Res","year":"2001"},{"key":"2026032606192029100_BIB2","first-page":"721","volume-title":"Nature","year":"1997"},{"key":"2026032606192029100_BIB3","first-page":"291","volume-title":"J Clin Invest","year":"2003"},{"key":"2026032606192029100_BIB4","first-page":"350","volume-title":"N Engl J Med","year":"2001"},{"key":"2026032606192029100_BIB5","first-page":"1","volume-title":"Nat Rev Immunol","year":"2003"},{"key":"2026032606192029100_BIB6","first-page":"55","volume-title":"Annu Rev Immunol","year":"2002"},{"key":"2026032606192029100_BIB7","first-page":"837","volume-title":"Am J Respir Cell Mol Biol","year":"2004"},{"key":"2026032606192029100_BIB8","first-page":"758","volume-title":"J Allergy Clin Immunol","year":"2002"},{"key":"2026032606192029100_BIB9","first-page":"945","volume-title":"Nat Rev Immunol","year":"2002"},{"key":"2026032606192029100_BIB10","first-page":"773","volume-title":"Nat Rev Immunol","year":"2002"},{"key":"2026032606192029100_BIB11","first-page":"133","volume-title":"Am J Respir Cell Mol Biol","year":"2003"},{"key":"2026032606192029100_BIB12","first-page":"2198","volume-title":"J Immunol","year":"2000"},{"key":"2026032606192029100_BIB13","first-page":"113","volume-title":"J Allergy Clin Immunol","year":"2003"},{"key":"2026032606192029100_BIB14","first-page":"281","volume-title":"J Pharmacol Exp Ther","year":"2000"},{"key":"2026032606192029100_BIB15","first-page":"161","volume-title":"Korean J Physiol Pharmacol","year":"2003"},{"key":"2026032606192029100_BIB16","first-page":"220","volume-title":"Inflamm Res","year":"2004"},{"key":"2026032606192029100_BIB17","first-page":"1715","volume-title":"J Biol Chem","year":"1999"},{"key":"2026032606192029100_BIB18","first-page":"17181","volume-title":"J Biol Chem","year":"2004"},{"key":"2026032606192029100_BIB19","first-page":"7053","volume-title":"J Immunol","year":"2004"},{"key":"2026032606192029100_BIB20","first-page":"295","volume-title":"J Pharmacol Methods","year":"1987"},{"key":"2026032606192029100_BIB21","first-page":"36","volume-title":"Anal Biochem","year":"1996"},{"key":"2026032606192029100_BIB22","first-page":"1272","volume-title":"Drug Metab Dispos","year":"1997"},{"key":"2026032606192029100_BIB23","first-page":"19","volume-title":"Anal Biochem","year":"2002"},{"key":"2026032606192029100_BIB24","first-page":"1198","volume-title":"J Appl Physiol","year":"2002"},{"key":"2026032606192029100_BIB25","first-page":"450","volume-title":"J Allergy Clin Immunol","year":"2002"},{"key":"2026032606192029100_BIB26","first-page":"7110","volume-title":"J Immunol","year":"1999"},{"key":"2026032606192029100_BIB27","first-page":"38","volume-title":"Nat Immunol","year":"2004"},{"key":"2026032606192029100_BIB28","first-page":"4283","volume-title":"J Immunol","year":"2001"},{"key":"2026032606192029100_BIB29","first-page":"87","volume-title":"Cell Immunol","year":"1998"},{"key":"2026032606192029100_BIB30","first-page":"4763","volume-title":"J Immunol","year":"1999"},{"key":"2026032606192029100_BIB31","first-page":"S269","volume-title":"J Allergy Clin Immunol","year":"2002"},{"key":"2026032606192029100_BIB32","first-page":"309","volume-title":"Respir Physiol Neurobiol","year":"2003"},{"key":"2026032606192029100_BIB33","first-page":"1161","volume-title":"Am J Respir Crit Care Med","year":"2002"},{"key":"2026032606192029100_BIB34","first-page":"596","volume-title":"Am J Respir Crit Care Med","year":"2004"},{"key":"2026032606192029100_BIB35","first-page":"329","volume-title":"Am J Respir Cell Mol Biol","year":"2002"},{"key":"2026032606192029100_BIB36","first-page":"801","volume-title":"Immunity","year":"2001"},{"key":"2026032606192029100_BIB37","first-page":"585","volume-title":"Am J Respir Cell Mol Biol","year":"2004"},{"key":"2026032606192029100_BIB38","first-page":"108","volume-title":"Nat Rev Immunol","year":"2001"},{"key":"2026032606192029100_BIB39","first-page":"1400","volume-title":"Am J Respir Crit Care Med","year":"2003"},{"key":"2026032606192029100_BIB40","first-page":"2477","volume-title":"J Immunol","year":"1999"},{"key":"2026032606192029100_BIB41","first-page":"1911","volume-title":"Blood","year":"2000"},{"key":"2026032606192029100_BIB42","first-page":"L1066","volume-title":"Am J Physiol Lung Cell Mol Physiol","year":"2002"},{"key":"2026032606192029100_BIB43","first-page":"779","volume-title":"J Clin Invest","year":"1999"},{"key":"2026032606192029100_BIB44","first-page":"L730","volume-title":"Am J Physiol Lung Cell Mol Physiol","year":"2003"},{"key":"2026032606192029100_BIB45","first-page":"844","volume-title":"J Appl Physiol","year":"2003"},{"key":"2026032606192029100_BIB46","first-page":"651","volume-title":"J Allergy Clin Immunol","year":"2000"},{"key":"2026032606192029100_BIB47","first-page":"6482","volume-title":"J Immunol","year":"2002"},{"key":"2026032606192029100_BIB48","first-page":"410","volume-title":"Am J Respir Cell Mol Biol","year":"2003"},{"key":"2026032606192029100_BIB49","first-page":"359","volume-title":"Antisense Nucleic Acid Drug Dev","year":"2000"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/171\/6\/571\/67488600\/ajrccm_171_6_571.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/171\/6\/571\/67488600\/ajrccm_171_6_571.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T10:19:26Z","timestamp":1774520366000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/171\/6\/571\/8538414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2005,3,15]]},"published-print":{"date-parts":[[2005,3,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.200408-1006oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2005,3]]},"published":{"date-parts":[[2005,3]]}}}