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• W2894969135 abstract "We have previously shown that reactive oxygen species (ROS) as prooxidants can activate Toll-like receptor 4 (TLR4) with the potential to initiate, propagate and maintain sterile inflammation of innate immunity, which plays a mediatory role in a host of human disease states. We now present new evidence that ROS can also activate TLR4 to counter the inflammatory phenotype by increasing the production of resolvin D1 (RvD1), which is a specialized anti-inflammatory and pro-resolving lipid mediator. We used primary murine peritoneal macrophages (pM) derived from both TLR4-WT and TLR4-KO mice as a cellular model. We used potassium peroxychromate (PPC) as a direct in vitro source of exogenous ROS. PPC treatment increased intracellular ROS levels, which decreased intracellular total antioxidant capacity, thus suggesting an enhanced cellular oxidative stress. PPC and LPS-EK (a TLR4-specific agonist) increased pro-inflammatory TNFα production with noeffect on IL-10, an anti-inflammatory cytokine. Treatment with the prooxidant increased the expression of 12 lipoxygenase (12-LOX) and 5-lipoxygenase (5-LOX) only in pM derived from TLR4 WT but not in pM from TLR4-KO mice. 5-LOX and 12-LOX are the key enzymes in the RvD1 biosynthetic pathway. In addition, PPC increased the expression of RvD1 receptor, a member of G-protein-coupled receptor only in pM from TLR4-WT mice. Our data support the involvement of TLR4-mediated oxidant-induced pro-inflammatory phenotypes that are in opposition to the production of anti-inflammatory/pro-resolution phenotypes in macrophages. Now, we show that through TLR4 activation, exogenous oxidants can play a role both in producing proinflammatory phenotypes at the same time that it enhances resolution of inflammation to maintain a state of cellular homeostasis and prevent tissue damage/disease." @default.
• W2894969135 created "2018-10-12" @default.
• W2894969135 creator A5039233620 @default.
• W2894969135 creator A5086664284 @default.
• W2894969135 date "2018-12-01" @default.
• W2894969135 modified "2023-09-25" @default.
• W2894969135 title "Role of Toll-like receptor 4/oxidant-coupled activation in regulating the biosynthesis of omega-3 polyunsaturated fatty acid derivative resolvin D1 in primary murine peritoneal macrophage" @default.
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• W2894969135 doi "https://doi.org/10.1016/j.bcp.2018.09.021" @default.
• W2894969135 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30287282" @default.
• W2894969135 hasPublicationYear "2018" @default.
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