Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1

被引：36

作者：

Haage, Verena ^{[1
]}

Elmadany, Nirmeen ^{[1
]}

Roll, Lars ^{[2
]}

Faissner, Andreas ^{[2
]}

Gutmann, David H. ^{[1
,3
]}

Semtner, Marcus ^{[1
]}

Kettenmann, Helmut ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, Helmholtz Assoc, Cellular Neurosci, Robert Rossle Str 10, D-13125 Berlin, Germany

[2] Ruhr Univ Bochum, Fak Biol & Biotechnol, Zellmorphol & Mol Neurobiol, D-44801 Bochum, Nordrhein Wastf, Germany

[3] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

来源：

BRAIN BEHAVIOR AND IMMUNITY | 2019年 / 81卷

关键词：

ECM protein Tenascin C; Microglia; TLR4; HDAC1; Phagocytosis; Early postnatal development; HISTONE DEACETYLASES 1; TOLL-LIKE RECEPTOR-4; NF-KAPPA-B; INNATE IMMUNITY; NEURAL STEM; MOUSE MODEL; CELLS; BRAIN; EXPRESSION; ACTIVATION;

D O I：

10.1016/j.bbi.2019.06.047

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tenascin C (Tnc) is an extracellular matrix glycoprotein, expressed in the CNS during development, as well as in the setting of inflammation, fibrosis and cancer, which operates as an activator of Toll-like receptor 4 (TLR4). Although TLR4 is highly expressed in microglia, the effect of Tnc on microglia has not been elucidated to date. Herein, we demonstrate that Tnc regulates microglial phagocytic activity at an early postnatal age (P4), and that this process is partially dependent on microglial TLR4 expression. We further show that Tnc regulates proinflammatory cytokine/chemokine production, chemotaxis and phagocytosis in primary microglia in a TLR4-dependent fashion. Moreover, Tnc induces histone-deacetylase 1 (HDAC1) expression in microglia, such that HDAC1 inhibition by MS-275 decreases Tnc-induced microglial IL-6 and TNF-alpha production. Finally, Tnc(-/-) cortical microglia have reduced HDAC1 expression levels at P4. Taken together, these findings establish Tnc as a regulator of microglia function during early postnatal development.

引用

页码：470 / 483

页数：14

共 90 条

[21] Skin wounds and severed nerves heal normally in mice lacking tenascin-C [J].