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Melatonin inhibits IL1β-induced MMP9 expression and activity in human umbilical vein endothelial cells by suppressing

Weiwei Qin1, Wenbao Lu, Hongwei Li

  • 1Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.

The Journal of Endocrinology
|May 24, 2012
PubMed

Insights

Melatonin protects endothelial cells from inflammatory damage by reducing MMP9 expression and permeability. This antioxidant molecule inhibits the NF-κB pathway, crucial for inflammatory responses.

Area of Science:

  • Endothelial Biology
  • Inflammation Research
  • Molecular Medicine

Background:

  • Matrix metalloproteinases (MMPs) contribute to inflammatory and degradative processes in diseases.
  • Interleukin 1 beta (IL1β) is a key inflammatory mediator affecting endothelial cells.
  • Endothelial barrier integrity is crucial for preventing pathological conditions.

Purpose of the Study:

  • To investigate the protective effects of melatonin on human umbilical vein endothelial cell (HUVEC) monolayer permeability.
  • To determine melatonin's role in regulating MMP9 expression induced by IL1β in HUVECs.
  • To elucidate the involvement of the nuclear factor-kappa B (NF-κB) pathway in IL1β-induced endothelial barrier disruption and melatonin's effect.

Main Methods:

  • HUVEC monolayer permeability assays using sodium fluorescein.
  • Analysis of MMP9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression.
  • Western blot analysis for vascular endothelial cadherin and occludin.
  • Assessment of NF-κB nuclear translocation via immunofluorescence or Western blot.

Main Results:

  • IL1β significantly increased MMP9 expression and HUVEC permeability.
  • Melatonin demonstrated a barrier-protective effect by downregulating MMP9 and upregulating TIMP-1.
  • Melatonin counteracted IL1β-induced decrease in vascular endothelial cadherin and occludin expression.
  • IL1β induced NF-κB nuclear translocation, which was significantly inhibited by melatonin.
  • Melatonin decreased MMP9 expression and activity via an NF-κB-dependent pathway.

Conclusions:

  • Melatonin effectively reduces IL1β-induced endothelial cell permeability.
  • Melatonin exerts its protective effects by inhibiting the NF-κB pathway, thereby decreasing MMP9 expression and activity.
  • Melatonin represents a potential therapeutic agent for conditions involving endothelial inflammation and barrier dysfunction.

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