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Cylindromatosis (CYLD) inhibits Streptococcus pneumonia-induced plasminogen activator inhibitor-1 expression via

Jing Wu1, Jing Zhao1, Jie Yu1

  • 1Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Biochemical and Biophysical Research Communications
|June 10, 2015
PubMed

Insights

Streptococcus pneumoniae (S. pneumoniae) lung infections involve plasminogen activator inhibitor-1 (PAI-1), regulated by cylindromatosis (CYLD). CYLD inhibits PAI-1 by deubiquitinating tumor necrosis factor receptor-associated factor 6 (TRAF-6).

Area of Science:

  • Immunology
  • Molecular Biology
  • Pulmonology

Background:

  • Streptococcus pneumoniae (S. pneumoniae) is a leading cause of community-acquired pneumonia.
  • S. pneumoniae infection is linked to plasminogen activator inhibitor-1 (PAI-1) expression, which mitigates acute lung injury.
  • Cylindromatosis (CYLD) negatively regulates S. pneumoniae-induced PAI-1 effects.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which CYLD regulates S. pneumoniae-induced PAI-1 expression.
  • To investigate the role of tumor necrosis factor receptor-associated factor 6 (TRAF-6) signaling in this pathway.

Main Methods:

  • Si-RNA mediated knockdown of TRAF-6.
  • Over-expression of wild-type (wt-) and mutated CYLD and TRAF-6.
  • Co-immunoprecipitation (co-IP) assays.
  • Confocal microscopy.

Main Results:

  • S. pneumoniae-induced PAI-1 expression is dependent on TRAF-6 signaling.
  • Knockdown of TRAF-6 significantly inhibited S. pneumoniae-induced PAI-1 expression.
  • CYLD directly associates with TRAF-6.
  • Over-expression of wt-CYLD inhibited TRAF-6 ubiquitination and PAI-1 expression, while mutated CYLD enhanced it.

Conclusions:

  • TRAF-6 mediates S. pneumoniae-induced PAI-1 expression.
  • CYLD inhibits PAI-1 expression by deubiquitinating TRAF-6.
  • These findings offer molecular insights into CYLD's role in S. pneumoniae-induced PAI-1 expression and potential acute lung injury modulation.
Keywords:
Cyindromatosis (CYLD)DeubiquitinationPAI-1Streptococcus pneumoniaeTRAF-6

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