Department of Cell-to-Cell Communication, Medical University of Lodz, Mazowiecka 6/8, 92- 215, Lodz, Poland.
An-Nan Hospital, China Medical University, Tainan, Taiwan.
BMC Neurosci. 2021 Jan 27;22(1):4. doi: 10.1186/s12868-021-00611-w.
Astrocytes are responsible for a broad range of functions that maintain homeostasis in the brain. However, their response to the pro-inflammatory cytokines released by activated microglia in various neurological pathologies may exacerbate neurodegenerative processes. Accumulating evidence suggests that omega-3 docosahexaenoic fatty acid (DHA) has an anti-inflammatory effect in various cell cultures studies and in a variety of neurological disorders. In this study we examined the mechanism involved in the inhibition of the pro-inflammatory response by DHA in astrocytes treated with IL-1β.
Activation of the transcription factors NF-κB and AP-1 was measured in IL-1β-treated primary astrocytes incubated with various concentrations of DHA. COX-2 and iNOS protein expression was determined by Western blot, and TNF-α and IL-6 secretion was measured using ELISA-based assays. DHA treatment inhibited translocation of p65NF-κB to the nucleus, significantly lowered p65NF-κB protein level and fluorescence of p65NF-κB in the nucleus, reduced dose-dependently IκB protein phosphorylation, and the binding of the AP-1 transcription factor members (c-Jun/c-Fos) to the specific TPA-response element (TRE) of DNA. In addition, the expression of pro-inflammatory COX-2 and iNOS proteins was downregulated and TNF-α and IL-6 secretion was also reduced.
These results indicate that DHA is a powerful factor that reduces the pro-inflammatory response in astrocytes. Consequently, successful introduction of DHA into the astrocyte membranes can attenuate neuroinflammation, which is a key factor of age-related neurodegenerative disorders.
星形胶质细胞负责维持大脑内环境稳定的广泛功能。然而，它们对各种神经病理学中激活的小胶质细胞释放的促炎细胞因子的反应可能会加剧神经退行性过程。越来越多的证据表明，ω-3 二十二碳六烯酸（DHA）在各种细胞培养研究和各种神经紊乱中具有抗炎作用。在这项研究中，我们研究了 DHA 抑制 IL-1β 处理的星形胶质细胞促炎反应的机制。
在用不同浓度的 DHA 孵育的 IL-1β 处理的原代星形胶质细胞中测量转录因子 NF-κB 和 AP-1 的激活。通过 Western blot 测定 COX-2 和 iNOS 蛋白表达，并通过 ELISA 测定 TNF-α 和 IL-6 的分泌。DHA 处理抑制了 p65NF-κB 向核内的易位，显著降低了 p65NF-κB 蛋白水平和核内 p65NF-κB 的荧光强度，剂量依赖性地降低了 IκB 蛋白磷酸化，并降低了 AP-1 转录因子成员（c-Jun/c-Fos）与特定 TPA 反应元件（TRE）的结合。此外，促炎 COX-2 和 iNOS 蛋白的表达下调，TNF-α 和 IL-6 的分泌也减少。
这些结果表明，DHA 是一种强大的因子，可降低星形胶质细胞的促炎反应。因此，成功地将 DHA 引入星形胶质细胞膜可以减轻神经炎症，这是与年龄相关的神经退行性疾病的关键因素。
