Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1

Verena Haage, Nirmeen Elmadany, Lars Roll, Andreas Faissner, David H. Gutmann, Marcus Semtner, Helmut Kettenmann

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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-α 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.

Original languageEnglish
Pages (from-to)470-483
Number of pages14
JournalBrain, Behavior, and Immunity
Volume81
DOIs
StatePublished - Oct 2019

Keywords

  • ECM protein Tenascin C
  • Early postnatal development
  • HDAC1
  • Microglia
  • Phagocytosis
  • TLR4

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