TY - JOUR
T1 - Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1
AU - Haage, Verena
AU - Elmadany, Nirmeen
AU - Roll, Lars
AU - Faissner, Andreas
AU - Gutmann, David H.
AU - Semtner, Marcus
AU - Kettenmann, Helmut
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - ECM protein Tenascin C
KW - Early postnatal development
KW - HDAC1
KW - Microglia
KW - Phagocytosis
KW - TLR4
UR - http://www.scopus.com/inward/record.url?scp=85068530771&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2019.06.047
DO - 10.1016/j.bbi.2019.06.047
M3 - Article
C2 - 31271872
AN - SCOPUS:85068530771
SN - 0889-1591
VL - 81
SP - 470
EP - 483
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -