{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:59:28Z","timestamp":1791352768274,"version":"4.3.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"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":[[2010,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypersensitivity pneumonitis is an interstitial lung disease that results from repeated pulmonary exposure to various organic Ags, including Saccharopolyspora rectivirgula, the causative agent of farmer\u2019s lung disease. Although the contributions of proinflammatory mediators to the disease pathogenesis are relatively well documented, the mechanism(s) involved in the initiation of proinflammatory responses against the causative microorganisms and the contribution of signaling molecules involved in the host immune defense have not been fully elucidated. In the current study, we found that S. \u00a0rectivirgula induces the activation of protein kinase D (PKD)1 in lung cells in vitro and in vivo. Activation of PKD1 by S. \u00a0rectivirgula was dependent on MyD88. Inhibition of PKD by pharmacological PKD inhibitor G\u00f66976 and silencing of PKD1 expression by small interfering RNA revealed that PKD1 is indispensable for S. \u00a0rectivirgula-mediated activation of MAPKs and NF-\u03baB and the expression of various proinflammatory cytokines and chemokines. In addition, compared with controls, mice pretreated with G\u00f66976 showed significantly suppressed alveolitis and neutrophil influx in bronchial alveolar lavage fluid and interstitial lung tissue, as well as substantially decreased myeloperoxidase activity in the lung after pulmonary exposure to S. \u00a0rectivirgula. These results demonstrate that PKD1 is essential for S. \u00a0rectivirgula-mediated proinflammatory immune responses and neutrophil influx in the lung. Our findings also imply the possibility that PKD1 is one of the critical factors that play a regulatory role in the development of hypersensitivity pneumonitis caused by microbial Ags and that inhibition of PKD1 activation could be an effective way to control microbial Ag-induced hypersensitivity pneumonitis.<\/jats:p>","DOI":"10.4049\/jimmunol.0903718","type":"journal-article","created":{"date-parts":[[2010,2,8]],"date-time":"2010-02-08T20:44:50Z","timestamp":1265661890000},"page":"3145-3156","source":"Crossref","is-referenced-by-count":46,"title":["Protein Kinase D1 Is Essential for the Proinflammatory Response Induced by Hypersensitivity Pneumonitis-Causing Thermophilic Actinomycetes\n                    <i>Saccharopolyspora rectivirgula<\/i>"],"prefix":"10.1093","volume":"184","author":[{"given":"Young-In","family":"Kim","sequence":"first","affiliation":[{"name":"Children\u2019s Foundation Research Center at Le Bonheur Children\u2019s Medical Center"},{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeoung-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Children\u2019s Foundation Research Center at Le Bonheur Children\u2019s Medical Center"},{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D","family":"Brand","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Medical Center , Memphis, TN 38104"},{"name":"Department of Molecular Sciences"},{"name":"Department of Medicine, University of Tennessee Health Science Center , Memphis, TN 38103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A","family":"Fitzpatrick","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ae-Kyung","family":"Yi","sequence":"additional","affiliation":[{"name":"Children\u2019s Foundation Research Center at Le Bonheur Children\u2019s Medical Center"},{"name":"Department of Pediatrics"},{"name":"Department of Molecular Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,3,15]]},"reference":[{"key":"2026012806310745100_r1","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/j.1398-9995.2009.01949.x","article-title":"Hypersensitivity pneumonitis.","volume":"64","author":"Girard","year":"2009","journal-title":"Allergy"},{"key":"2026012806310745100_r2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S0761-8425(04)71418-7","article-title":"Clinical and immunopathological aspects of hypersensitivity pneumonitis].","volume":"21","author":"Lacasse","year":"2004","journal-title":"Rev. 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