Connections of annexin A1 and translocator protein-18 kDa on toll like receptor stimulated BV-2 cells

Lorena Pantaleao, Gustavo Henrique Rocha, Chris Reutelingsperger, Manoela Tiago, Silvya Stucchi Maria-Engler, Egle Solito, Sandra P. Farsky*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Web of Science)

Abstract

Background: Annexin A1 (ANXA1) and Translocator Protein-18KDa (TSPO) down-regulate neuroinflammation. We investigated the role of recombinant ANXA1 (rANXA) on TSPO functions on Toll Like Receptor (TLR) activated microglia. Methods: BV-2 cells (murine microglia), were stimulated by E. coli Lipopolysaccharide (LPS) and treated with rANXA1 in order to measure TSPO expression and inflammatory parameters. Anti-sense ANXA1 and TLR4 and TSPO shRNA, as well as pharmacological treatments, were employed to assess the mechanisms involved. Results: LPS-stimulated BV-2 cells caused overexpression of TSPO, which was inhibited by: pharmacological blockade of TLR4 or TLR4 mRNA silencing; inhibition of myeloid differentiation primary response gene 88 (MyD88) dimerization; or blocking of nuclear factor kappa B (NF-kappa B) activation. rANXA1 treatment impaired LPS-induced TSPO upregulation by down-modulating MyD88 and NF-kappa B signaling; the effect was abolished by WRW4, an antagonist of formyl peptide receptor 2 (FPR2). rANXA1 treatment also downregulated interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) secretion in LPS-stimulated BV-2 cells. TSPO knockdown in BV-2 cells augmented LPS-induced TNFa secretion and abolished the inhibitory effect of rANXA1 on TNF alpha secretion evoked by LPS. Conclusions: exogenous ANXA1 down-modulates LPS-induced TSPO via MyD-88/NF-kappa B pathways, and constitutive TSPO is pivotal for the control of ANXA1 on TNF alpha secretion. TSPO actions may be involved with the mechanisms of ANXA1 on inflammatory brain diseases.
Original languageEnglish
Pages (from-to)282-290
Number of pages9
JournalExperimental Cell Research
Volume367
Issue number2
DOIs
Publication statusPublished - 15 Jun 2018

Keywords

  • Neuroinflammation
  • NF-kappa B
  • MyD88
  • LPS
  • FPR2
  • TNF alpha
  • BLOOD-BRAIN-BARRIER
  • IN-VIVO
  • MICROGLIAL ACTIVATION
  • INFLAMMATION
  • RESOLUTION
  • NEUROINFLAMMATION
  • DISRUPTION
  • INHIBITION
  • PATHWAY
  • MODEL

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