Reduced inflammatory response in cigarette smoke exposed Mrp1/Mdr1a/1b deficient mice.
Reduced inflammatory response in cigarette smoke exposed Mrp1/Mdr1a/1b deficient mice.
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DOI：
10.1186/1465-9921-8-49
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发表时间：
2007-07-07
影响因子：
5.8
通讯作者：
Kerstjens HA
中科院分区：
文献类型：
--
作者：
van der Deen M;Timens W;Timmer-Bosscha H;van der Strate BW;Scheper RJ;Postma DS;de Vries EG;Kerstjens HA
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. We examined whether triple knock-out (TKO) mice lacking the genes for Mrp1 and Mdr1a/1b 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. 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 (P < 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 (P < 0.05) with a same trend for G-CSF (P < 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. Mrp1/Mdr1a/1b 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 Mrp1/Mdr1a/1b 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.
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影响因子：
24.3
作者：
Willemse, BWM;ten Hacken, NHT;Timens, W
通讯作者：
Timens, W
影响因子：
4.4
作者：
Schultz, MJ;Wijnholds, J;van der Poll, T
通讯作者：
van der Poll, T
影响因子：
4.4
作者：
van de Ven, Rieneke;de Jong, Mariska C.;Scheper, Rik J.
通讯作者：
Scheper, Rik J.
影响因子：
15.9
作者：
Wijnholds, J;de Lange, ECM;Borst, P
通讯作者：
Borst, P
影响因子：
82.9
作者：
Wijnholds, J;Evers, R;Borst, P
通讯作者：
Borst, P