{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:08:48Z","timestamp":1790719728750,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2007,7,7]],"date-time":"2007-07-07T00:00:00Z","timestamp":1183766400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Tobacco smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD), though the mechanisms of its toxicity are still unclear. The ABC transporters multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein (P-gp\/MDR1) extrude a wide variety of toxic substances across cellular membranes and are highly expressed in bronchial epithelium. Their impaired function may contribute to COPD development by diminished detoxification of noxious compounds in cigarette smoke.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We examined whether triple knock-out (TKO) mice lacking the genes for <jats:italic>Mrp1<\/jats:italic> and <jats:italic>Mdr1a\/1b<\/jats:italic> are more susceptible to develop COPD features than their wild-type (WT) littermates. TKO and WT mice (six per group) were exposed to 2 cigarettes twice daily by nose-only exposure or room air for 6 months. Inflammatory infiltrates were analyzed in lung sections, cytokines and chemokines in whole lung homogenates, emphysema by mean linear intercept. Multiple linear regression analysis with an interaction term was used to establish the statistical significances of differences.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>TKO mice had lower levels of interleukin (IL)-7, KC (mouse IL-8), IL-12p70, IL-17, TNF-alpha, G-CSF, GM-CSF and MIP-1-alpha than WT mice independent of smoke exposure (<jats:italic>P<\/jats:italic> &lt; 0.05). IL-1-alpha, IL-6, IL-8, IL-13, IL-17, TNF-alpha, G-CSF, GM-CSF and MCP-1 increased after smoke exposure in both groups, but the increase in IL-8 was lower in TKO than WT mice (<jats:italic>P<\/jats:italic> &lt; 0.05) with a same trend for G-CSF (<jats:italic>P<\/jats:italic> &lt; 0.10). Smoke-induced increase in pulmonary inflammatory cells in WT mice was almost absent in TKO mice. The mean linear intercept was not different between groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>\n              <jats:italic>Mrp1\/Mdr1a\/1b<\/jats:italic> knock-out mice have a reduced inflammatory response to cigarette smoke. In addition, the expression levels of several cytokines and chemokines were also lower in lungs of <jats:italic>Mrp1\/Mdr1a\/1b<\/jats:italic> knock-out mice independent of smoke exposure. Further studies are required to determine whether dysfunction of MRP1 and\/or P-gp contribute to the pathogenesis of COPD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1465-9921-8-49","type":"journal-article","created":{"date-parts":[[2007,7,7]],"date-time":"2007-07-07T18:31:11Z","timestamp":1183833071000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Reduced inflammatory response in cigarette smoke exposed Mrp1\/Mdr1a\/1b deficient mice"],"prefix":"10.1186","volume":"8","author":[{"given":"Margaretha","family":"van der Deen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Timens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetty","family":"Timmer-Bosscha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry W","family":"van der Strate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik J","family":"Scheper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirkje S","family":"Postma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth G","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huib A","family":"Kerstjens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,7,7]]},"reference":[{"key":"587_CR1_587","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1126\/science.1360704","volume":"258","author":"SP Cole","year":"1992","unstructured":"Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG: Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.\nScience 1992, 258:1650\u20131654.","journal-title":"Science"},{"key":"587_CR2_587","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.toxlet.2004.12.008","volume":"156","author":"D Balayssac","year":"2005","unstructured":"Balayssac D, Authier N, Cayre A, Coudore F: Does inhibition of P-glycoprotein lead to drug-drug interactions?\nToxicol Lett 2005, 156:319\u2013329.","journal-title":"Toxicol Lett"},{"key":"587_CR3_587","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1177\/002215549804600411","volume":"46","author":"JM Brechot","year":"1998","unstructured":"Brechot JM, Hurbain I, Fajac A, Daty N, Bernaudin JF: Different pattern of MRP localization in ciliated and basal cells from human bronchial epithelium.\nJ Histochem Cytochem 1998, 46:513\u2013517.","journal-title":"J Histochem Cytochem"},{"key":"587_CR4_587","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1136\/jcp.55.5.332","volume":"55","author":"GL Scheffer","year":"2002","unstructured":"Scheffer GL, Pijnenborg AC, Smit EF, Muller M, Postma DS, Timens W, van der Valk P, de Vries EG, Scheper RJ: Multidrug resistance related molecules in human and murine lung.\nJ Clin Pathol 2002, 55:332\u2013339.","journal-title":"J Clin Pathol"},{"key":"587_CR5_587","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/1465-9921-6-59","volume":"6","author":"M van der Deen","year":"2005","unstructured":"van der Deen M, de Vries EG, Timens W, Scheper RJ, Timmer-Bosscha H, Postma DS: ATP-binding cassette (ABC) transporters in normal and pathological lung.\nRespir Res 2005, 6:59.","journal-title":"Respir Res"},{"key":"587_CR6_587","doi-asserted-by":"publisher","first-page":"27846","DOI":"10.1074\/jbc.M102453200","volume":"276","author":"EM Leslie","year":"2001","unstructured":"Leslie EM, Ito K, Upadhyaya P, Hecht SS, Deeley RG, Cole SP: Transport of the beta -O-glucuronide conjugate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by the multidrug resistance protein 1 (MRP1). 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