Gamma-Linolenic Acid Inhibits Inflammatory Responses by Regulating NF-κB and AP-1 Activation in Lipopolysaccharide-Induced RAW 264.7 Macrophages
Gamma-Linolenic Acid Inhibits Inflammatory Responses by Regulating NF-κB and AP-1 Activation in Lipopolysaccharide-Induced RAW 264.7 Macrophages
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DOI：
10.1007/s10753-009-9157-8
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发表时间：
2010-02-01
期刊：
影响因子：
5.1
通讯作者：
Liu, Kai-Li
中科院分区：
文献类型：
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作者：
Chang, Cheng-Sue;Sun, Hai-Lun;Liu, Kai-Li
γ-亚麻酸（GLA）是n-6多不饱和脂肪酸家族的成员，并且可以通过酶δ-6-去饱和酶由亚油酸（LA）合成。GLA补充剂的治疗价值已被证明，但GLA在健康益处中的作用背后的分子机制尚不清楚。在这项研究中，我们评估了GLA与LA对脂多糖（LPS）诱导的炎症反应的影响，并进一步探讨了GLA在小鼠RAW 264.7巨噬细胞中药理学特性的分子机制。GLA显著抑制LPS诱导的诱导型一氧化氮合酶、前白细胞介素-1 β和环氧合酶-2的蛋白表达以及一氧化氮的产生和细胞内谷胱甘肽水平。LA在抑制LPS诱导的炎症介质方面不如GLA有效。GLA和LA处理均显著抑制LPS诱导的I κ B-α降解、I κ B-α磷酸化和核p65蛋白表达。此外，LA和GLA显著降低LPS诱导的核因子-κ B（NF-κ B）和激活蛋白-1（AP-1）核蛋白-DNA结合亲和力和报告基因活性。外源性添加GLA而非LA显著降低LPS诱导的磷酸化细胞外信号调节激酶（ERK）1/2和c-Jun N-末端激酶（JNK）-1的表达。我们的数据表明，GLA通过抑制LPS诱导的RAW 264.7巨噬细胞中的氧化应激和ERK和JNK信号转导途径来灭活NF-κ B和AP-1，从而抑制炎症反应。
Gamma linolenic acid (GLA) is a member of the n-6 family of polyunsaturated fatty acids and can be synthesized from linoleic acid (LA) by the enzyme delta-6-desaturase. The therapeutic values of GLA supplementation have been documented, but the molecular mechanism behind the action of GLA in health benefits is not clear. In this study, we assessed the effect of GLA with that of LA on lipopolysaccharide (LPS)-induced inflammatory responses and further explored the molecular mechanism underlying the pharmacological properties of GLA in mouse RAW 264.7 macrophages. GLA significantly inhibited LPS-induced protein expression of inducible nitric oxide synthase, pro-interleukin-1 beta, and cyclooxygenase-2 as well as nitric oxide production and the intracellular glutathione level. LA was less potent than GLA in inhibiting LPS-induced inflammatory mediators. Both GLA and LA treatments dramatically inhibited LPS-induced I kappa B-alpha degradation, I kappa B-alpha phosphorylation, and nuclear p65 protein expression. Moreover, LPS-induced nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) nuclear protein-DNA binding affinity and reporter gene activity were significantly decreased by LA and GLA. Exogenous addition of GLA but not LA significantly reduced LPS-induced expression of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK)-1. Our data suggest that GLA inhibits inflammatory responses through inactivation of NF-kappa B and AP-1 by suppressed oxidative stress and signal transduction pathway of ERK and JNK in LPS-induced RAW 264.7 macrophages.