PMID- 30635405
OWN - NLM
STAT- MEDLINE
DCOM- 20190520
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 294
IP  - 10
DP  - 2019 Mar 8
TI  - Oxidation of methionine residues in human apolipoprotein A-I generates a potent 
      pro-inflammatory molecule.
PG  - 3634-3646
LID - 10.1074/jbc.RA118.005663 [doi]
AB  - Amyloid deposits of apolipoprotein A-I (apoA-I) and inflammation are common in 
      atherosclerotic arteries. In this study, we investigated the interplay between 
      oxidation of apoA-I methionine residues (Met(O)-ApoA-I), a known amyloidogenic 
      modification of apoA-I, and the inflammatory response of immune cells. Soluble 
      pre-fibrillar Met(O)-ApoA-I, but not apoA-I, induced intracellular accumulation 
      of pro-interleukin (IL)-1beta and secretion of the pro-inflammatory cytokines tumor 
      necrosis factor alpha (TNFalpha) and IL-6 in mouse bone marrow-derived macrophages 
      (BMDMs) and human primary monocytes. Additionally, secretion of mature IL-1beta was 
      also activated in human monocytes. The pro-inflammatory activity of Met(O)-ApoA-I 
      was Toll-like receptor 4 (TLR4)-dependent and CD36-independent and was solely 
      determined by oxidation of apoA-I methionine residues, in particular Met-86 and 
      Met-148. In contrast, amyloid fibrils or reconstituted high-density lipoproteins 
      (HDLs) generated from Met(O)-ApoA-I did not induce cytokine production in BMDMs. 
      Although lipid-free Met(O)-ApoA-I remained functional in extracting lipids from 
      cells and generating HDL, it gained strong pro-inflammatory properties that may 
      aggravate local inflammation in the arteries and atherosclerosis. Our study 
      indicates that oxidation of apoA-I methionine residues produces a potent 
      danger-associated molecular pattern capable of stimulating pro-inflammatory 
      cytokine secretion at levels similar to those induced by known 
      pathogen-associated molecular patterns, such as lipopolysaccharide.
CI  - (c) 2019 Witkowski et al.
FAU - Witkowski, Andrzej
AU  - Witkowski A
AUID- ORCID: 0000-0002-0442-4586
AD  - From the UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, 
      California 94609.
FAU - Carta, Sonia
AU  - Carta S
AD  - the Cell Biology Unit, Ospedale Policlinico San Martino, 16132 Genova, Italy, 
      and.
FAU - Lu, Rui
AU  - Lu R
AD  - Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, Japan.
FAU - Yokoyama, Shinji
AU  - Yokoyama S
AD  - Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, Japan.
FAU - Rubartelli, Anna
AU  - Rubartelli A
AD  - the Cell Biology Unit, Ospedale Policlinico San Martino, 16132 Genova, Italy, 
      and.
FAU - Cavigiolio, Giorgio
AU  - Cavigiolio G
AD  - From the UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, 
      California 94609, gcavigiolio@chori.org.
LA  - eng
GR  - R01 HL113059/HL/NHLBI NIH HHS/United States
GR  - S10 OD018070/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190111
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Toll-Like Receptor 4)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Apolipoprotein A-I/*chemistry/*metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Methionine/*metabolism
MH  - Mice
MH  - Oxidation-Reduction
MH  - Toll-Like Receptor 4/metabolism
PMC - PMC6416445
OTO - NOTNLM
OT  - DAMP
OT  - Toll-like receptor (TLR)
OT  - amyloid
OT  - apolipoprotein
OT  - apolipoprotein A-I
OT  - atherosclerosis
OT  - cytokine induction
OT  - cytokines
OT  - inflammation
OT  - interleukin
OT  - macrophage
OT  - methionine oxidation
OT  - oxidation-reduction (redox)
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2019/01/13 06:00
MHDA- 2019/05/21 06:00
PMCR- 2020/03/08
CRDT- 2019/01/13 06:00
PHST- 2018/08/31 00:00 [received]
PHST- 2018/12/27 00:00 [revised]
PHST- 2020/03/08 00:00 [pmc-release]
PHST- 2019/01/13 06:00 [pubmed]
PHST- 2019/05/21 06:00 [medline]
PHST- 2019/01/13 06:00 [entrez]
AID - S0021-9258(20)38988-2 [pii]
AID - RA118.005663 [pii]
AID - 10.1074/jbc.RA118.005663 [doi]
PST - ppublish
SO  - J Biol Chem. 2019 Mar 8;294(10):3634-3646. doi: 10.1074/jbc.RA118.005663. Epub 
      2019 Jan 11.