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Published on: January 30, 2014

Dihydropyrimidinase-like 3 regulates the inflammatory response of activated microglia

J Manivannan1, S S W Tay, E-A Ling

  • 1Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD10, 4 Medical Drive, Singapore 117597, Singapore.

Neuroscience
|August 31, 2013
PubMed

Insights

Dihydropyrimidinase-like 3 (Dpysl3) is crucial for microglial activation, migration, and phagocytosis. Inhibiting Dpysl3 reduces neuroinflammation by suppressing pro-inflammatory responses in microglia.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are the primary immune cells in the central nervous system (CNS).
  • Microglia activation involves producing pro-inflammatory cytokines and phagocytosis.
  • The role of dihydropyrimidinase-like 3 (Dpysl3) in microglial inflammatory responses is largely unknown.

Purpose of the Study:

  • To investigate the expression pattern of Dpysl3 in microglia.
  • To elucidate the role of Dpysl3 in microglial activation and neuroinflammation.

Main Methods:

  • Microarray and immunohistochemical analyses were used to determine Dpysl3 expression in rat brains.
  • In vitro studies utilized BV-2 microglia treated with lipopolysaccharide (LPS).
  • Small interfering RNA (siRNA) was used to knock down Dpysl3 expression.

Main Results:

  • Dpysl3 expression was predominantly observed in ameboid microglia in developing rat brains and induced by LPS in vitro.
  • Knockdown of Dpysl3 suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines (IL-1β, TNF-α).
  • Dpysl3 knockdown inhibited microglial migration, altered actin cytoskeleton organization, and impaired phagocytic activity, consequently reducing neuroinflammation.

Conclusions:

  • Dpysl3 plays a significant role in regulating microglial activation, migration, and phagocytosis.
  • Targeting Dpysl3 may represent a novel therapeutic strategy for reducing neuroinflammation.
Keywords:
4′,6-diamidino-2-phenylindolAMCCNSCRMPsDAPIDpysl3F-actinIL-1βLPSNF-κBNOPBSPhosphate-buffered salineRMCRT-PCRReverse Transcription–Polymerase Chain ReactionTNF-αameboid microglial cellscentral nervous systemcollapsin response mediator proteinsdihydropyrimidinase like 3filamentous actiniNOSinducible nitric oxide synthaseinterleukin-1 betalipopolysaccharidemicrogliamigrationnitric oxidenuclear factor kappa-light-chain-enhancer of activated B cellsphagocytosisproinflammatory cytokinesramified microglial cellssiRNAsmall interfering RNAtumor necrosis factor-alpha

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