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Published on: January 7, 2019

Double-stranded RNA induces MMP-9 gene expression in HaCaT keratinocytes by tumor necrosis factor-α

Andreas Voss1, Kirsten Gescher, Andreas Hensel

  • 1Institute of Immunology, Helmholtz Centre for Infection Research, Inhoffenstr 7, D-38124 Braunschweig, Germany.

Inflammation & Allergy Drug Targets
|March 25, 2011
PubMed

Insights

Poly (I:C) triggers matrix metallo-proteinase-9 (MMP-9) expression in skin cells via specific signaling pathways. This finding is crucial for understanding inflammation and tissue injury during antiviral responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Dermatology

Background:

  • Viral double-stranded RNA (dsRNA) and its analog poly (I:C) are recognized by cellular pathways, initiating inflammatory gene expression.
  • Matrix metallo-proteinases (MMPs) play roles in tissue remodeling and inflammation.

Purpose of the Study:

  • To investigate the specific induction of matrix metallo-proteinase-9 (MMP-9) by poly (I:C) in HaCaT keratinocytes.
  • To elucidate the signaling pathways and cellular mechanisms involved in poly (I:C)-induced MMP-9 expression.

Main Methods:

  • HaCaT keratinocytes were treated with poly (I:C).
  • Pharmacological inhibitors targeting NF-κB, p38 MAPK, PI-3K, vacuolar H(+)-ATPase (bafilomycin A1), and lysosomes (chloroquine) were used.
  • Cycloheximide was employed to assess protein synthesis dependence.
  • TNFα stimulation was performed to evaluate its effect on MMP-9 expression.

Main Results:

  • Poly (I:C) specifically induced MMP-9 gene expression in HaCaT keratinocytes.
  • NF-κB, p38 MAPK, and PI-3K signaling pathways were involved in this induction.
  • MMP-9 induction was sensitive to bafilomycin A1 and chloroquine, suggesting involvement of vacuolar and lysosomal pathways.
  • Cycloheximide partially inhibited MMP-9 expression, indicating a role for de novo protein synthesis.
  • TNFα significantly promoted poly (I:C)-induced MMP-9 gene expression.

Conclusions:

  • Poly (I:C) induces MMP-9 expression in keratinocytes through NF-κB, p38 MAPK, and PI-3K signaling.
  • Vacuolar/lysosomal pathways and partial protein synthesis dependence are implicated in MMP-9 induction.
  • TNFα plays a key role in amplifying MMP-9 expression.
  • MMP-9 may contribute to tissue injury during antiviral responses.

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