The role of PPARγ in carbon nanotube-elicited granulomatous lung inflammation.
The role of PPARγ in carbon nanotube-elicited granulomatous lung inflammation.
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DOI：
10.1186/1465-9921-14-7
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发表时间：
2013-01-23
影响因子：
5.8
通讯作者：
Thomassen MJ
中科院分区：
文献类型：
--
作者：
Huizar I;Malur A;Patel J;McPeek M;Dobbs L;Wingard C;Barna BP;Thomassen MJ
尽管肉芽肿炎症是许多疾病过程的核心特征，但人们对肉芽肿形成和持续存在的细胞机制知之甚少。碳纳米颗粒可以是制造产品或环境产品，与肉芽肿性疾病有关。本文利用先前描述的碳纳米颗粒肉芽肿模型来解决过氧化物酶体增殖物激活受体γ（PPARγ）（一种核转录因子和炎症细胞因子的负调节因子）是否可能在肉芽肿性肺病中发挥作用的问题。 PPARγ 在健康个体的肺泡巨噬细胞中持续表达，但在结节病（一种典型的肉芽肿性疾病）患者的肺泡巨噬细胞中表达降低。我们之前对巨噬细胞特异性 PPARγ KO 小鼠的研究揭示了与野生型小鼠相比，固有炎症性肺部环境，促炎细胞因子水平升高。基于这些观察结果，我们假设，通过 MWCNT 滴注诱导患有肉芽肿的动物的肺泡巨噬细胞中 PPARγ 的表达会受到抑制。野生型 C57Bl/6 和巨噬细胞特异性 PPARγ KO 小鼠接受多壁碳纳米管 (MWCNT)（100 μg）的口咽滴注。滴注后 60 天获取支气管肺泡灌洗 (BAL) 细胞、BAL 液和肺组织，用于分析肉芽肿组织学和促炎细胞因子（骨桥蛋白、CCL2 和干扰素 γ [IFN-γ] mRNA 和蛋白表达）。在野生型小鼠中，MWCNT 滴注 60 天后，肉芽肿动物的肺泡巨噬细胞 PPARγ 表达和活性显着降低。在巨噬细胞特异性 PPARγ KO 小鼠中，在 MWCNT 注射后 60 天，PPARγ KO 小鼠的肉芽肿形成范围比野生型更广泛，在 MWCNT 暴露后 60 天，PPARγ KO 小鼠的肺组织、激光显微切割的肺肉芽肿和 BAL 细胞/液体中促炎细胞因子的表达也有所升高。总体而言，数据表明 PPARγ 缺乏会促进炎症和肉芽肿形成，表明 PPARγ 作为慢性炎症的负调节因子。肉芽肿性炎症。
Although granulomatous inflammation is a central feature of many disease processes, cellular mechanisms of granuloma formation and persistence are poorly understood. Carbon nanoparticles, which can be products of manufacture or the environment, have been associated with granulomatous disease. This paper utilizes a previously described carbon nanoparticle granuloma model to address the issue of whether peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear transcription factor and negative regulator of inflammatory cytokines might play a role in granulomatous lung disease. PPARγ is constitutively expressed in alveolar macrophages from healthy individuals but is depressed in alveolar macrophages of patients with sarcoidosis, a prototypical granulomatous disease. Our previous study of macrophage-specific PPARγ KO mice had revealed an intrinsically inflammatory pulmonary environment with an elevated pro-inflammatory cytokines profile as compared to wild-type mice. Based on such observations we hypothesized that PPARγ expression would be repressed in alveolar macrophages from animals bearing granulomas induced by MWCNT instillation. Wild-type C57Bl/6 and macrophage-specific PPARγ KO mice received oropharyngeal instillations of multiwall carbon nanotubes (MWCNT) (100 μg). Bronchoalveolar lavage (BAL) cells, BAL fluids, and lung tissues were obtained 60 days post-instillation for analysis of granuloma histology and pro-inflammatory cytokines (osteopontin, CCL2, and interferon gamma [IFN-γ] mRNA and protein expression. In wild-type mice, alveolar macrophage PPARγ expression and activity were significantly reduced in granuloma-bearing animals 60 days after MWCNT instillation. In macrophage-specific PPARγ KO mice, granuloma formation was more extensive than in wild-type at 60 days after MWCNT instillation. PPARγ KO mice also demonstrated elevated pro-inflammatory cytokine expression in lung tissue, laser-microdissected lung granulomas, and BAL cells/fluids, at 60 days post MWCNT exposure. Overall, data indicate that PPARγ deficiency promotes inflammation and granuloma formation, suggesting that PPARγ functions as a negative regulator of chronic granulomatous inflammation.
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DOI：
10.1165/rcmb.2010-0401oc
发表时间：
2011-10-01
影响因子：
6.4
作者：
Huizar, Isham;Malur, Anagha;Thomassen, Mary Jane
通讯作者：
Thomassen, Mary Jane
DOI：
10.1164/rccm.200402-249oc
发表时间：
2004-12-15
影响因子：
24.7
作者：
Newman, LS;Rose, CS;Cherniack, R
通讯作者：
Cherniack, R
影响因子：
3.3
作者：
DEVERGNE, O;EMILIE, D;GALANAUD, P
通讯作者：
GALANAUD, P
影响因子：
4.4
作者：
Malur, Anagha;Mccoy, Almedia J.;Thomassen, Mary Jane
通讯作者：
Thomassen, Mary Jane
DOI：
10.1152/ajplung.00453.2001
发表时间：
2002-06-01
影响因子：
4.9
作者：
Maus, UA;Koay, MA;Lohmeyer, J
通讯作者：
Lohmeyer, J