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Isolation of Primary Murine Brain Microvascular Endothelial Cells
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TLR2 Ligand Pam3CSK4 Regulates MMP-2/9 Expression by MAPK/NF-κB Signaling Pathways in Primary Brain Microvascular

Hongyan Zhu1,2,3,4, Rongrong Dai5, Youquan Zhou6

  • 1Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, 650093, Yunnan Province, China.

Neurochemical Research
|August 9, 2018
PubMed

Insights

Toll-like receptor-2 (TLR2) activation upregulates matrix metalloproteinase-9 (MMP-9) via ERK1/2 and JNK pathways in brain endothelial cells. However, NF-κB signaling negatively regulates TLR2

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Blood-brain barrier (BBB) destruction is implicated in neurological diseases.
  • Brain microvascular endothelial cells (BMECs) form the BBB and express matrix metalloproteinases-2/9 (MMP-2/9) and toll-like receptor-2 (TLR2).
  • The regulatory role of TLR2 in MMP-2/9 expression within BMECs remains unclear.

Purpose of the Study:

  • To investigate whether TLR2 activation influences MMP-2/9 expression and tight junction integrity in BMECs.
  • To elucidate the specific signaling pathways (MAPKs, NF-κB) involved in TLR2-mediated regulation of MMP-2/9 in BMECs.

Main Methods:

  • BMECs were treated with Pam3CSK4 to activate TLR2.
  • Quantitative real-time PCR and western blotting were used to measure MMP-2/9 and tight junction expression.
  • Inhibitors of mitogen-activated protein kinases (MAPKs) and NF-κB were employed to dissect signaling pathways.

Main Results:

  • Pam3CSK4 upregulated MMP-9 while downregulating MMP-2 and tight junction expression in BMECs.
  • TLR2 activation induced phosphorylation of MAPKs and NF-κB signaling pathways.
  • MMP-9 upregulation was dependent on ERK1/2 and JNK pathways, whereas NF-κB inhibition increased both MMP-2 and MMP-9 expression.

Conclusions:

  • TLR2 activation upregulates MMP-9 expression through ERK1/2 and JNK signaling in BMECs.
  • The NF-κB pathway negatively regulates TLR2's effect on MMP-2 and MMP-9 expression in BMECs.
  • This study reveals a novel molecular mechanism underlying MMP regulation in BMECs, offering insights into BBB integrity.
Keywords:
Brain microvascular endothelial cellsMatrix metalloproteinaseMitogen-activated protein kinasesPam3CSK4Toll-like receptor-2

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