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低浓度脂肪酸可诱导正常人星形胶质细胞中白细胞介素-8水平早期升高。

Low-Concentrations of Fatty Acids Induce an Early Increase in IL-8 Levels in Normal Human Astrocytes.

作者信息

Dobri Ana-Maria, Codrici Elena, Popescu Ionela-Daniela, Albulescu Lucian, Fertig Emanuel Tudor, Enciu Ana-Maria, Tanase Cristiana, Hinescu Mihail E

机构信息

"Victor Babes" National Institute of Pathology, 050096 Bucharest, Romania.

Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.

出版信息

Metabolites. 2022 Apr 6;12(4):329. doi: 10.3390/metabo12040329.

Abstract

Fatty acids (FAs) have been shown to exhibit a pro-inflammatory response in various cell types, but astrocytes have been mostly overlooked. FAs, both saturated and unsaturated, have previously been shown to induce pro-inflammatory responses in astrocytes at high concentrations of hundreds of µg/mL. SSO (Sulfo--succinimidyl Oleate sodium), an inhibitor of FA translocase CD36, has been shown to prevent inflammation in the mouse brain by acting on local microglia and infiltrating monocytes. Our hypothesis was that SSO treatment would also impact astrocyte pro-inflammatory response to FA. In order to verify our assumption, we evaluated the expression of pro- and anti-inflammatory cytokines in normal human astrocyte cell culture pre-treated (or not) with SSO, and then exposed to low concentrations of both saturated (palmitic acid) and unsaturated (oleic acid) FAs. As a positive control for astrocyte inflammation, we used fibrillary amyloid. Neither Aβ 1-42 nor FAs induced CD36 protein expression in human astrocytes in cell culture At low concentrations, both types of FAs induced IL-8 protein secretion, and this effect was specifically inhibited by SSO pre-treatment. In conclusion, low concentrations of oleic acid are able to induce an early increase in IL-8 expression in normal human astrocytes, which is specifically downregulated by SSO.

摘要

脂肪酸(FAs)已被证明在多种细胞类型中表现出促炎反应,但星形胶质细胞大多被忽视。饱和脂肪酸和不饱和脂肪酸此前已被证明在数百微克/毫升的高浓度下可诱导星形胶质细胞产生促炎反应。脂肪酸转运蛋白CD36的抑制剂磺基琥珀酰亚胺油酸钠(SSO)已被证明可通过作用于局部小胶质细胞和浸润的单核细胞来预防小鼠大脑中的炎症。我们的假设是,SSO处理也会影响星形胶质细胞对脂肪酸的促炎反应。为了验证我们的假设,我们评估了在预先用(或未用)SSO处理的正常人星形胶质细胞培养物中促炎和抗炎细胞因子的表达,然后将其暴露于低浓度的饱和脂肪酸(棕榈酸)和不饱和脂肪酸(油酸)中。作为星形胶质细胞炎症的阳性对照,我们使用了纤维状淀粉样蛋白。在细胞培养中,β淀粉样蛋白1-42和脂肪酸均未诱导人星形胶质细胞中CD36蛋白的表达。在低浓度下,两种类型的脂肪酸均诱导白细胞介素-8蛋白分泌,而这种作用被SSO预处理特异性抑制。总之,低浓度的油酸能够诱导正常人星形胶质细胞中白细胞介素-8表达的早期增加,而SSO可特异性下调这种增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a30/9031664/4d03920bdf92/metabolites-12-00329-g001.jpg

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