Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun 130021, China.
VIP Integrated Department, School and Hospital of Stomatology, Jilin University, Changchun 130021, China.
Biomed Res Int. 2020 Sep 14;2020:4616308. doi: 10.1155/2020/4616308. eCollection 2020.
The brain is in many ways an immunologically and pharmacologically privileged site because of the blood-brain barrier (BBB). But for chronic peripheral inflammation, inflammatory signals can be transmitted from the peripheral system into the central nervous system (CNS) through multiple channels and result in neuroinflammation. Leptomeningeal cells that form the BBB can trigger one signaling pathway by releasing cytokines to transmit inflammatory signals. Besides, the Janus kinase (JAK) family may have a certain function in the activation of leptomeninges. In the present study, we try to use coniferyl aldehyde (CA), a natural anti-inflammatory phenolic compound, to inhibit this inflammatory process and elucidate the underlying molecular mechanisms.
Secretion of proinflammatory cytokines (TNF-, IL-1, and IL-6) significantly increased after incubation with . Moreover, TNF-, IL-1, and IL-6 levels were upregulated, and the JAK2 signaling was enhanced in leptomeningeal cells in a conditioned medium from activated macrophages, which leads to the immune response in microglia. However, this inflammatory effect of leptomeningeal cells was reversed by CA administration, accompanied by the decreased immune response in microglia. The western blot assay revealed that JAK2 phosphorylation was suppressed in leptomeningeal cells treated with CA.
This study demonstrates that activated macrophages by markedly induce the release of proinflammatory cytokines (TNF-, IL-1, and IL-6) from leptomeningeal cells, thereby activating the JAK2 signaling pathway and subsequently enhancing immune responses in microglia in the CNS. CA effectively inhibits the inflammatory effect of leptomeningeal cells via suppressing the JAK2 signaling pathway.
由于血脑屏障（BBB）的存在，大脑在许多方面都是一个具有免疫和药理学优势的部位。但是，对于慢性外周炎症，炎症信号可以通过多种途径从外周系统传递到中枢神经系统（CNS），并导致神经炎症。形成 BBB 的软脑膜细胞可以通过释放细胞因子触发一条信号通路，从而传递炎症信号。此外，Janus 激酶（JAK）家族在软脑膜的激活中可能具有一定的功能。在本研究中，我们试图使用松柏醛（CA），一种天然的抗炎性酚类化合物，来抑制这种炎症过程，并阐明潜在的分子机制。
用 孵育后，促炎细胞因子（TNF-、IL-1 和 IL-6）的分泌显著增加。此外，在激活的巨噬细胞条件培养基中，IL-1 和 IL-6 水平上调，JAK2 信号增强，导致小胶质细胞的免疫反应，从而导致软脑膜细胞中的炎症反应。然而，CA 的给药逆转了软脑膜细胞的这种炎症作用，伴随着小胶质细胞中的免疫反应降低。Western blot 分析表明，CA 处理的软脑膜细胞中 JAK2 磷酸化受到抑制。
本研究表明， 激活的巨噬细胞显著诱导软脑膜细胞释放促炎细胞因子（TNF-、IL-1 和 IL-6），从而激活 JAK2 信号通路，并随后增强 CNS 中小胶质细胞的免疫反应。CA 通过抑制 JAK2 信号通路有效抑制软脑膜细胞的炎症作用。
