PMID- 25184331
OWN - NLM
STAT- MEDLINE
DCOM- 20150514
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 9
DP  - 2014
TI  - The oxidative stress product carboxyethylpyrrole potentiates TLR2/TLR1 
      inflammatory signaling in macrophages.
PG  - e106421
LID - 10.1371/journal.pone.0106421 [doi]
LID - e106421
AB  - Oxidative stress is key in the pathogenesis of several diseases including 
      age-related macular degeneration (AMD), atherosclerosis, diabetes, and 
      Alzheimer's disease. It has previously been established that a lipid peroxidation 
      product, carboxyethylpyrrole (CEP), accumulates in the retinas of AMD patients. 
      Retinal infiltrating macrophages also accumulate in the retinas of both AMD 
      patients and in a murine model of AMD. We therefore investigated the ability of 
      CEP-adducts to activate innate immune signaling in murine bone-marrow derived 
      macrophages (BMDMs). We found that CEP specifically synergizes with low-dose 
      TLR2-agonists (but not agonists for other TLRs) to induce production of 
      inflammatory cytokines. Moreover, CEP selectively augments TLR2/TLR1-signaling 
      instead of TLR2/TLR6-signaling. These studies uncover a novel synergistic 
      inflammatory relationship between an endogenously produced oxidation molecule and 
      a pathogen-derived product, which may have implications in the AMD disease 
      process and other oxidative stress-driven pathologies.
FAU - Saeed, Ali M
AU  - Saeed AM
AD  - Sheila and David Fuente Program in Cancer Biology, University of Miami Miller 
      School of Medicine, Miami, Florida, United States of America.
FAU - Duffort, Stephanie
AU  - Duffort S
AD  - Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami 
      Miller School of Medicine, Miami, Florida, United States of America.
FAU - Ivanov, Dmitry
AU  - Ivanov D
AD  - Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami 
      Miller School of Medicine, Miami, Florida, United States of America.
FAU - Wang, Hua
AU  - Wang H
AD  - Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United 
      States of America.
FAU - Laird, James M
AU  - Laird JM
AD  - Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United 
      States of America.
FAU - Salomon, Robert G
AU  - Salomon RG
AD  - Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United 
      States of America.
FAU - Cruz-Guilloty, Fernando
AU  - Cruz-Guilloty F
AD  - Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami 
      Miller School of Medicine, Miami, Florida, United States of America; Department 
      of Microbiology and Immunology, University of Miami Miller School of Medicine, 
      Miami, Florida, United States of America.
FAU - Perez, Victor L
AU  - Perez VL
AD  - Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami 
      Miller School of Medicine, Miami, Florida, United States of America; Department 
      of Microbiology and Immunology, University of Miami Miller School of Medicine, 
      Miami, Florida, United States of America.
LA  - eng
GR  - P30 EY014801/EY/NEI NIH HHS/United States
GR  - R01 GM021249/GM/NIGMS NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - NIH P30EY14801/EY/NEI NIH HHS/United States
GR  - NIH R01-GM21249/GM/NIGMS NIH HHS/United States
GR  - R01 EY016813/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140903
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Pyrroles)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr6 protein, mouse)
RN  - 0 (Toll-Like Receptor 1)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 6)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation
MH  - Humans
MH  - Immunity, Innate/drug effects
MH  - Inflammation/genetics/immunology/pathology
MH  - Lipid Peroxidation/drug effects
MH  - Macrophages/drug effects/immunology
MH  - Macular Degeneration/genetics/*immunology/pathology
MH  - Mice
MH  - Oxidative Stress/drug effects
MH  - Pyrroles/*administration & dosage/metabolism
MH  - Signal Transduction/drug effects
MH  - Toll-Like Receptor 1/*biosynthesis/genetics
MH  - Toll-Like Receptor 2/*biosynthesis/genetics
MH  - Toll-Like Receptor 6/biosynthesis/genetics
PMC - PMC4153630
COIS- Competing Interests: This study was partly supported by a Bank of America N.A. 
      Trustee Award Program. The mouse model for dry AMD described in this study is 
      protected for commercialization by SKS Ocular. R.G.S. and V.L.P. are 
      co-inventors. There are no further patents, products in development or marketed 
      products to declare. The CEP model patent name and number is the following: 
      "Non-human model of autoimmune disease", number 20090155243. This does not alter 
      the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials, as detailed online in the guide for authors.
EDAT- 2014/09/04 06:00
MHDA- 2015/05/15 06:00
PMCR- 2014/09/03
CRDT- 2014/09/04 06:00
PHST- 2014/03/18 00:00 [received]
PHST- 2014/07/29 00:00 [accepted]
PHST- 2014/09/04 06:00 [entrez]
PHST- 2014/09/04 06:00 [pubmed]
PHST- 2015/05/15 06:00 [medline]
PHST- 2014/09/03 00:00 [pmc-release]
AID - PONE-D-14-11405 [pii]
AID - 10.1371/journal.pone.0106421 [doi]
PST - epublish
SO  - PLoS One. 2014 Sep 3;9(9):e106421. doi: 10.1371/journal.pone.0106421. eCollection 
      2014.