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.
(Less)
- author
- Svensson, Daniel
LU
; Lagerstedt, Jens O.
LU
; Nilsson, Bengt Olof
LU
and Del Giudice, Rita
LU
- organization
- publishing date
- 2017-09-15
- 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
- pmid:28919413
- 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
- 2025-01-07 21:51:15
@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}},
keywords = {{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}},
doi = {{10.1016/j.bbrc.2017.09.072}},
volume = {{493}},
year = {{2017}},
}