Lipopolysaccharide differentially regulates microglial trk receptor and neurotrophin expression

✍ Scribed by Stella Elkabes; Lang Peng; Ira B. Black

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 80 KB
• Volume: 54
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19981001)54:1<117::aid-jnr12>3.0.co;2-4

✦ Synopsis

Activated brain microglia play a pivotal role in inflammatory and degenerative disorders, mediating immune function and producing toxic and trophic agents. We previously reported that microglia express neurotrophins and that neurotrophin-3 (NT-3) increases microglial proliferation and phagocytosis, processes associated with cellular activation. However, mechanisms regulating responsiveness to NT-3 and expression of NT-3 in activated microglia remain undefined. To investigate mechanisms governing microglial responsiveness to neurotrophins, we determined whether microglia express trk C, the high-affinity receptor for NT-3, and whether the inflammatory agent lipopolysaccharide (LPS) regulates receptor expression. Trk C mRNA was expressed by unstimulated microglia, and both trk C mRNA and protein were dramatically increased by LPS. In contrast, expression of trk A, the high-affinity receptor for nerve growth factor (NGF), was down-regulated by LPS. Consequently, the same stimulus differentially influences responsiveness of microglia to distinct trophins. In addition, LPS induced microglial NT-3 expression, suggesting that increases in both the ligand and receptor modulate NT-3 effects on microglia. Regulation was specific, since brain-derived neurotrophic factor (BDNF) and NT-4/5 expression were unaltered by LPS. In sum, our findings raise the possibility that microglial NT-3 regulates their response to inflammation through autocrine mechanisms: LPS modulates both trk C and NT-3 which, in turn, regulate microglial function. J.