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Jens Lagerstedt

Associate professor

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Apolipoprotein A-I attenuates LL-37-induced endothelial cell cytotoxicity

Author

  • Daniel Svensson
  • Jens O. Lagerstedt
  • Bengt Olof Nilsson
  • Rita Del Giudice

Summary, in English

The human cathelicidin peptide LL-37 has antimicrobial and anti-biofilm functions, but LL-37 may also damage the host by triggering inflammation and exerting a cytotoxic effect, thereby reducing host cell viability. Human plasma mitigates LL-37-induced host cell cytotoxicity but the underlying mechanisms are not completely understood. Apolipoprotein A-I (ApoA-I) is a plasma protein endowed with atheroprotective effects. Here, we investigate the interaction between ApoA-I and LL-37 by biochemical techniques, and furthermore assess if ApoA-I protects against LL-37-evoked cytotoxicity in human umbilical vein endothelial cells (HUVEC). Our results demonstrated that ApoA-I effectively binds LL-37. The binding of ApoA-I to LL-37 resulted in a structural rearrangement of the protein, but this interaction did not cause lower ApoA-I stability. Recombinant ApoA-I protected against LL-37-induced cytotoxicity in HUVEC and endogenous ApoA-I knockdown in HepG2 cells made the cells more sensitive to LL-37-evoked cytotoxicity. We conclude that ApoA-I physically interacts with LL-37 and antagonizes LL-37-induced down-regulation of endothelial cell viability suggesting that this mechanism counteracts endothelial cell dysfunction.

Department/s

  • Vascular Physiology
  • Medical Protein Science
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2017-09-15

Language

English

Pages

71-76

Publication/Series

Biochemical and Biophysical Research Communications

Volume

493

Issue

1

Document type

Journal article

Publisher

Elsevier

Topic

  • Medicinal Chemistry

Keywords

  • Antimicrobial peptide (AMP)
  • ApoA-I
  • Cathelicidin
  • Endothelium
  • Host defence peptide
  • Innate immunity

Status

Published

Research group

  • Vascular Physiology
  • Medical Protein Science

ISBN/ISSN/Other

  • ISSN: 0006-291X