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Exp Cell Res. 2018 Jun 15;367(2):282-290. doi: 10.1016/j.yexcr.2018.04.008. Epub 2018 Apr 9.

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

Author information

1
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 580 Bl. 13B, São Paulo 05508-900, Brazil.
2
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, 616 6200 MD, 6211 CH Maastricht, The Netherlands.
3
William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University, EC1M 6BQ, Charterhouse Square, London, United Kingdom.
4
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 580 Bl. 13B, São Paulo 05508-900, Brazil. Electronic address: sfarsky@usp.br.

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 κB (NF-κB) activation. rANXA1 treatment impaired LPS-induced TSPO upregulation by down-modulating MyD88 and NF-κB signaling; the effect was abolished by WRW4, an antagonist of formyl peptide receptor 2 (FPR2). rANXA1 treatment also downregulated interleukin 1β (IL-1β) and tumor necrosis factor-α (TNFα) secretion in LPS-stimulated BV-2 cells. TSPO knockdown in BV-2 cells augmented LPS-induced TNFα secretion and abolished the inhibitory effect of rANXA1 on TNFα secretion evoked by LPS.

CONCLUSIONS:

exogenous ANXA1 down-modulates LPS-induced TSPO via MyD-88/NF-κB pathways, and constitutive TSPO is pivotal for the control of ANXA1 on TNFα secretion. TSPO actions may be involved with the mechanisms of ANXA1 on inflammatory brain diseases.

KEYWORDS:

FPR2; LPS; MyD88; NF-κB; Neuroinflammation; TNFα

PMID:
29649428
DOI:
10.1016/j.yexcr.2018.04.008
[Indexed for MEDLINE]

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