{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T23:40:29Z","timestamp":1776814829807,"version":"3.51.2"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"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":[[2006,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Spleen tyrosine kinase (Syk) is important for Fc and B-cell receptor\u2013mediated signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the activity of a specific Syk inhibitor (R406) on mast cell activation in vitro and on the development of allergen-induced airway hyperresponsiveness (AHR) and inflammation in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>AHR and inflammation were induced after 10 d of allergen (ovalbumin [OVA]) exposure exclusively via the airways and in the absence of adjuvant. This approach was previously established to be IgE, Fc\u03b5RI, and mast cell dependent. Alternatively, mice were passively sensitized with OVA-specific IgE, followed by limited airway challenge. In vitro, the inhibitor was added to cultures of IgE-sensitized bone marrow\u2013derived mast cells (BMMCs) before cross-linking with allergen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The inhibitor prevented OVA-induced degranulation of passively IgE-sensitized murine BMMCs and inhibited the production of interleukin (IL)-13, tumor necrosis factor \u03b1, IL-2, and IL-6 in these sensitized BMMCs. When administered in vivo, R406 inhibited AHR, which developed in BALB\/c mice exposed to aerosolized 1% OVA for 10 consecutive d (20 min\/d), as well as pulmonary eosinophilia and goblet cell metaplasia. A similar inhibition of AHR was demonstrated in mice passively sensitized with OVA-specific IgE and exposed to limited airway challenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study delineates a functional role for Syk in the development of mast cell\u2013 and IgE-mediated AHR and airway inflammation, and these results indicate that inhibition of Syk may be a target in the treatment of allergic asthma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200503-361oc","type":"journal-article","created":{"date-parts":[[2005,9,28]],"date-time":"2005-09-28T20:34:12Z","timestamp":1127939652000},"page":"56-63","source":"Crossref","is-referenced-by-count":83,"title":["Inhibition of Spleen Tyrosine Kinase Prevents Mast Cell Activation and Airway Hyperresponsiveness"],"prefix":"10.1093","volume":"173","author":[{"given":"Shigeki","family":"Matsubara","sequence":"first","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiming","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuyuki","family":"Takeda","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan E.","family":"Loader","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polly","family":"Pine","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esteban S.","family":"Masuda","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuaki","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph J.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azzeddine","family":"Dakhama","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin W.","family":"Gelfand","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and Rigel Pharmaceuticals, Inc., San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2006,1,1]]},"reference":[{"key":"2026040105500762600_BIB1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1056\/NEJM200102013440507","volume":"344","year":"2001","journal-title":"N Engl J Med"},{"key":"2026040105500762600_BIB2","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1056\/NEJMoa012705","volume":"346","year":"2002","journal-title":"N Engl J Med"},{"key":"2026040105500762600_BIB3","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.2174\/1381612043384538","volume":"10","year":"2004","journal-title":"Curr Pharm Des"},{"key":"2026040105500762600_BIB4","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.it.2004.03.005","volume":"25","year":"2004","journal-title":"Trends Immunol"},{"key":"2026040105500762600_BIB5","doi-asserted-by":"crossref","first-page":"F1","DOI":"10.1084\/jem.194.1.F1","volume":"194","year":"2001","journal-title":"J Exp Med"},{"key":"2026040105500762600_BIB6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1084\/jem.184.1.71","volume":"184","year":"1996","journal-title":"J Exp Med"},{"key":"2026040105500762600_BIB7","first-page":"2595","volume":"13","year":"1996","journal-title":"Oncogene"},{"key":"2026040105500762600_BIB8","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1517\/13543784.13.7.743","volume":"13","year":"2004","journal-title":"Expert Opin Investig Drugs"},{"key":"2026040105500762600_BIB9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0014-2999(02)01534-0","volume":"443","year":"2002","journal-title":"Eur J Pharmacol"},{"key":"2026040105500762600_BIB10","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1124\/jpet.103.052316","volume":"306","year":"2003","journal-title":"J Pharmacol Exp Ther"},{"key":"2026040105500762600_BIB11","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1172\/JCI115651","volume":"89","year":"1992","journal-title":"J Clin Invest"},{"key":"2026040105500762600_BIB12","doi-asserted-by":"crossref","first-page":"6398","DOI":"10.4049\/jimmunol.172.10.6398","volume":"172","year":"2004","journal-title":"J Immunol"},{"key":"2026040105500762600_BIB13","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1172\/JCI118560","volume":"97","year":"1996","journal-title":"J Clin Invest"},{"key":"2026040105500762600_BIB14","first-page":"A754","volume":"2","year":"2005","journal-title":"Proc Am Thorac Soc"},{"key":"2026040105500762600_BIB15","doi-asserted-by":"crossref","first-page":"4599","DOI":"10.1073\/pnas.081021898","volume":"98","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026040105500762600_BIB16","doi-asserted-by":"crossref","first-page":"12762","DOI":"10.1074\/jbc.271.22.12762","volume":"271","year":"1996","journal-title":"J Biol Chem"},{"key":"2026040105500762600_BIB17","doi-asserted-by":"crossref","first-page":"5792","DOI":"10.4049\/jimmunol.166.9.5792","volume":"166","year":"2001","journal-title":"J Immunol"},{"key":"2026040105500762600_BIB18","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2165\/00063030-200418060-00007","volume":"18","year":"2004","journal-title":"BioDrugs"},{"key":"2026040105500762600_BIB19","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.4049\/jimmunol.169.2.1028","volume":"169","year":"2002","journal-title":"J Immunol"},{"key":"2026040105500762600_BIB20"},{"key":"2026040105500762600_BIB21","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.4049\/jimmunol.162.4.2087","volume":"162","year":"1999","journal-title":"J Immunol"},{"key":"2026040105500762600_BIB22","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1073\/pnas.94.12.6358","volume":"94","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026040105500762600_BIB23","doi-asserted-by":"crossref","first-page":"5387","DOI":"10.1093\/emboj\/19.20.5387","volume":"19","year":"2000","journal-title":"EMBO J"},{"key":"2026040105500762600_BIB24","doi-asserted-by":"crossref","first-page":"9107","DOI":"10.1073\/pnas.89.19.9107","volume":"89","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026040105500762600_BIB25","doi-asserted-by":"crossref","first-page":"23318","DOI":"10.1016\/S0021-9258(19)49465-9","volume":"268","year":"1993","journal-title":"J Biol Chem"},{"key":"2026040105500762600_BIB26","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1016\/S0021-9258(17)41945-4","volume":"269","year":"1994","journal-title":"J Biol Chem"},{"key":"2026040105500762600_BIB27","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.4049\/jimmunol.152.11.5429","volume":"152","year":"1994","journal-title":"J Immunol"},{"key":"2026040105500762600_BIB28","doi-asserted-by":"crossref","first-page":"8613","DOI":"10.1016\/S0021-9258(18)42487-8","volume":"267","year":"1992","journal-title":"J Biol Chem"},{"key":"2026040105500762600_BIB29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0092-8674(94)90334-4","volume":"76","year":"1994","journal-title":"Cell"},{"key":"2026040105500762600_BIB30","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S1074-7613(02)00303-5","volume":"16","year":"2002","journal-title":"Immunity"},{"key":"2026040105500762600_BIB31","doi-asserted-by":"crossref","first-page":"846","DOI":"10.4049\/jimmunol.170.2.846","volume":"170","year":"2003","journal-title":"J Immunol"},{"key":"2026040105500762600_BIB32","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1165\/ajrcmb.12.4.7695919","volume":"12","year":"1995","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026040105500762600_BIB33","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.4049\/jimmunol.169.4.2061","volume":"169","year":"2002","journal-title":"J Immunol"},{"key":"2026040105500762600_BIB34","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1165\/ajrcmb.21.4.3659","volume":"21","year":"1999","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026040105500762600_BIB35","doi-asserted-by":"crossref","first-page":"5183","DOI":"10.4049\/jimmunol.166.8.5183","volume":"166","year":"2001","journal-title":"J Immunol"},{"key":"2026040105500762600_BIB36","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1084\/jem.186.3.449","volume":"186","year":"1997","journal-title":"J Exp Med"},{"key":"2026040105500762600_BIB37","first-page":"L263","volume":"266","year":"1994","journal-title":"Am J Physiol"},{"key":"2026040105500762600_BIB38","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1084\/jem.192.3.455","volume":"192","year":"2000","journal-title":"J Exp Med"},{"key":"2026040105500762600_BIB39","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jaci.2004.03.033","volume":"114","year":"2004","journal-title":"J Allergy Clin Immunol"},{"key":"2026040105500762600_BIB40","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jaci.2004.03.034","volume":"114","year":"2004","journal-title":"J Allergy Clin Immunol"},{"key":"2026040105500762600_BIB41","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.cyto.2004.08.007","volume":"28","year":"2004","journal-title":"Cytokine"},{"key":"2026040105500762600_BIB42","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1126\/science.282.5397.2258","volume":"282","year":"1998","journal-title":"Science"},{"key":"2026040105500762600_BIB43","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nri1438","volume":"4","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"2026040105500762600_BIB44","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nm1081","volume":"10","year":"2004","journal-title":"Nat Med"},{"key":"2026040105500762600_BIB45","doi-asserted-by":"crossref","first-page":"4979","DOI":"10.4049\/jimmunol.174.8.4979","volume":"174","year":"2005","journal-title":"J Immunol"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/173\/1\/56\/67404788\/ajrccm_173_1_56.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/173\/1\/56\/67404788\/ajrccm_173_1_56.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T09:50:19Z","timestamp":1775037019000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/173\/1\/56\/8528078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1,1]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2006,1,1]]},"published-print":{"date-parts":[[2006,1,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.200503-361oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2006,1]]},"published":{"date-parts":[[2006,1,1]]}}}