Coniferyl Aldehyde Inhibits the Inflammatory Effects of Leptomeningeal Cells by Suppressing the JAK2 Signaling. (15th September 2020)

• Record Type: Journal Article
• Authors: Wang, Yao; Gao, Yajun; Li, Xue; Sun, Xiaolin; Wang, Zhanqi; Wang, Hanchi; Nie, Ran; Yu, Weixian; Zhou, Yanmin
• Other Names: Oliveira Mauro S. Academic Editor.
• Is Part Of: BioMed research international. Volume 2020(2020)
• Publication Date: 2020-09-15
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2020/4616308
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : Background . 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. Results . Secretion of proinflammatory cytokines (TNF- α, IL-1 β, and IL-6) significantly increased after incubation with P. gingivalis . Moreover, TNF- α, IL-1 β, 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. Conclusions . This study demonstrates that activated macrophages by P. gingivalis markedly induce the release of proinflammatory cytokines (TNF- α, IL-1 β, 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.