Activation‑induced upregulation of MMP9 in mast cells is a positive feedback mediator for mast cell activation

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Lin Xu1, Zhijian Cai2, Fei Yang2

  • 1Department of Otolaryngology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

Molecular Medicine Reports
|March 6, 2017
PubMed

Insights

Matrix metalloproteinase-9 (MMP9) is upregulated in activated mast cells, a key factor in allergic rhinitis (AR). Inhibiting MMP9 or its signaling pathways reduces mast cell activation, offering new therapeutic targets for AR.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Activated mast cells play a crucial role in allergic rhinitis (AR) pathogenesis.
  • Matrix metalloproteinase-9 (MMP9) is a pro-inflammatory enzyme implicated in immune responses.
  • The specific role of MMP9 in mast cell activation was previously unclear.

Purpose of the Study:

  • To investigate the involvement of MMP9 in mast cell activation.
  • To elucidate the signaling pathways regulating MMP9 expression in activated mast cells.
  • To explore the therapeutic potential of targeting MMP9 in AR.

Main Methods:

  • Mast cells were activated using phorbol ester and ionomycin.
  • MMP9 protein and mRNA expression levels were measured.
  • ERK and AKT signaling pathways were inhibited.
  • IL-4 signaling was modulated using IL-4 and neutralizing antibodies.

Main Results:

  • Mast cell activation led to increased MMP9 protein and mRNA expression.
  • Inhibition of ERK and AKT pathways attenuated MMP9 upregulation.
  • Inhibition of MMP9 activity or expression suppressed mast cell activation.
  • IL-4 treatment reduced MMP9 upregulation, while IL-4 blockade enhanced it.

Conclusions:

  • MMP9 is upregulated in activated mast cells via ERK and AKT signaling.
  • MMP9 plays a critical role in mast cell activation.
  • Targeting MMP9 presents a novel therapeutic strategy for allergic rhinitis.

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