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

Svensson, Daniel LU ; Lagerstedt, Jens O. LU ; Nilsson, Bengt Olof LU and Del Giudice, Rita LU (2017) In Biochemical and Biophysical Research Communications 493(1). p.71-76
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antimicrobial peptide (AMP), ApoA-I, Cathelicidin, Endothelium, Host defence peptide, Innate immunity
in
Biochemical and Biophysical Research Communications
volume
493
issue
1
pages
71 - 76
publisher
Elsevier
external identifiers
  • scopus:85029552786
  • wos:000413134200012
ISSN
0006-291X
DOI
10.1016/j.bbrc.2017.09.072
language
English
LU publication?
yes
id
ae3fac7a-daf5-40df-869d-96dd4a003e61
date added to LUP
2017-10-04 10:27:59
date last changed
2018-02-09 14:36:06
@article{ae3fac7a-daf5-40df-869d-96dd4a003e61,
  abstract     = {<p>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.</p>},
  author       = {Svensson, Daniel and Lagerstedt, Jens O. and Nilsson, Bengt Olof and Del Giudice, Rita},
  issn         = {0006-291X},
  keyword      = {Antimicrobial peptide (AMP),ApoA-I,Cathelicidin,Endothelium,Host defence peptide,Innate immunity},
  language     = {eng},
  month        = {09},
  number       = {1},
  pages        = {71--76},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Apolipoprotein A-I attenuates LL-37-induced endothelial cell cytotoxicity},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2017.09.072},
  volume       = {493},
  year         = {2017},
}