The oxidative stress product carboxyethylpyrrole potentiates TLR2/TLR1 inflammatory signaling in macrophages.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Saeed, AM; Duffort, S; Ivanov, D; Wang, H; Laird, JM; Salomon, RG; Cruz-Guilloty, F; Perez, VL
Published Date
- 2014
Published In
Volume / Issue
- 9 / 9
Start / End Page
- e106421 -
PubMed ID
- 25184331
Pubmed Central ID
- 25184331
Electronic International Standard Serial Number (EISSN)
- 1932-6203
Digital Object Identifier (DOI)
- 10.1371/journal.pone.0106421
Language
- eng
Conference Location
- United States