Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARβ/δ ligand GW0742
Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARβ/δ ligand GW0742
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DOI：
10.1007/s00011-007-7157-4
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发表时间：
2008-07-01
影响因子：
6.7
通讯作者：
Kilgore, K. S.
中科院分区：
文献类型：
--
作者：
Haskova, Z.;Hoang, B.;Kilgore, K. S.
目的：在脂多糖（LPS）诱导的肺部炎症模型中，利用选择性过氧化物酶体增殖物激活受体β/δ（PPARβ/δ）配体（GW0742）明确PPARβ/δ激活的抗炎作用。
方法：在诱导LPS介导的肺部炎症之前，用PPARβ/δ激动剂GW0742对雄性BALB/c小鼠预处理3天。分析支气管肺泡灌洗液（BALF）中炎症细胞的流入以及促炎介质的水平。还收集BALF来源的炎症细胞进行mRNA分析。
结果：用GW0742预处理导致白细胞向肺内募集显著减少。在接受GW0742处理的动物（30mg/kg）中，BALF中促炎细胞因子白细胞介素 - 6（IL - 6）、白细胞介素 - 1β（IL - 1β）和肿瘤坏死因子α（TNFα）的蛋白质和mRNA水平显著降低。在接受GW0742处理的动物的BALF中，粒细胞巨噬细胞集落刺激因子（GM - CSF）也显著降低，GM - CSF是中性粒细胞趋化性（通过其对TNFα和其他细胞因子/趋化因子的下游作用）、激活和存活的主要调节因子。
结论：本研究表明，在LPS诱导的肺部炎症模型中，PPARβ/δ的激活减轻了炎症程度，因此可能代表一种治疗炎症介导的疾病的新治疗方法。
Objective: To define the anti-inflammatory effects of PPAR beta/8 delta activation by use of the selective PPAR beta/delta ligand (GW0742) in a model of lipopolysaccharide (LPS)-induced pulmonary inflammation.Methods: Male BALB/c mice were pretreated for three days with the PPAR beta/delta agonist, GW0742, prior to induction of LPS-mediated pulmonary inflammation. Bronchial alveolar lavage fluid (BALF) was analyzed for inflammatory cell influx and for levels of pro-inflammatory mediators. BALF derived inflammatory cells were also collected for mRNA analysis.Results: Pretreatment with GW0742 resulted in a significant decrease in leukocyte recruitment into the pulmonary space. Protein and mRNA levels of the pro-inflammatory cytokines IL-6, IL-1 beta and TNF alpha in BALF were found to be significantly decreased in GW0742-treated animals (30mg/kg). A significant decrease in granulocyte macrophage-colony stimulating factor (GM-CSF), a major regulator of neutrophil chemotaxis (via its downstream actions on TNF alpha and other cytokines/chemokines), activation and survival, was also noted in the BALF levels of GW0742-treated animals.Conclusions: The present study demonstrates that activation of PPAR beta/delta attenuates the degree of inflammation in a model of LPS-induced pulmonary inflammation and may therefore represent a novel therapeutic approach for the treatment of inflammation-mediated pathologies.