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Toll-Like Receptor 4–Mediated Nuclear Factor Kappa B Activation Is Essential for Sensing Exogenous Oxidants to Propagate and Maintain Oxidative/Nitrosative Cellular Stress : Toll-Like Receptor 4-Mediated Nuclear Factor Kappa B Activation Is Essential for Sensing Exogenous Oxidants to Propagate and Maintain Oxidative/Nitrosative Cellular Stress
DC Field | Value | Language |
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dc.contributor.author | Karki, Rajendra | - |
dc.contributor.author | Igwe, Orisa J. | - |
dc.date.accessioned | 2024-05-16T01:59:59Z | - |
dc.date.available | 2024-05-16T01:59:59Z | - |
dc.date.created | 2023-05-08 | - |
dc.date.created | 2023-05-08 | - |
dc.date.issued | 2013-09 | - |
dc.identifier.citation | PLoS ONE, Vol.8 No.9, p. e73840 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://hdl.handle.net/10371/203068 | - |
dc.description.abstract | The mechanism(s) by which cells can sense exogenous oxidants that may contribute to intracellular oxidative/nitrosative stress is not clear. The objective of this study was to determine how cells might respond to exogenous oxidants to potentially initiate, propagate and/or maintain inflammation associated with many human diseases through NF-kappa B activation. First, we used HEK-Blue cells that are stably transfected with mouse toll-like receptor 4 (mTLR4) or mouse TLR2. These cells also express optimized secreted embryonic alkaline phosphatase (SEAP) reporter gene under the control of a promoter inducible by NF-kappa B transcription factor. These cells were challenged with their respective receptor-specific ligands, different pro-oxidants and/or inhibitors that act at different levels of the receptor signaling pathways. A neutralizing antibody directed against TLR4 inhibited responses to both TLR4-specific agonist and a prooxidant, which confirmed that both agents act through TLR4. We used the level of SEAP released into the culture media due to NF-kappa B activation as a measure of TLR4 or TLR2 stimulation. Pro-oxidants evoked increased release of SEAP from HEK-Blue mTLR4 cells at a much lower concentration compared with release from the HEK-Blue mTLR2 cells. Specific TLR4 signaling pathway inhibitors and oxidant scavengers (anti-oxidants) significantly attenuated oxidant-induced SEAP release by TLR4 stimulation. Furthermore, a novel pro-oxidant that decays to produce the same reactants as activated phagocytes induced inflammatory pain responses in the mouse orofacial region with increased TLR4 expression, and IL-1 beta and TNF alpha tissue levels. EUK-134, a synthetic serum-stable scavenger of oxidative species decreased these effects. Our data provide in vitro and related in vivo evidence that exogenous oxidants can induce and maintain inflammation by acting mainly through a TLR4-dependent pathway, with implications in many chronic human ailments. | - |
dc.language | 영어 | - |
dc.publisher | Public Library of Science | - |
dc.title | Toll-Like Receptor 4–Mediated Nuclear Factor Kappa B Activation Is Essential for Sensing Exogenous Oxidants to Propagate and Maintain Oxidative/Nitrosative Cellular Stress | - |
dc.title.alternative | Toll-Like Receptor 4-Mediated Nuclear Factor Kappa B Activation Is Essential for Sensing Exogenous Oxidants to Propagate and Maintain Oxidative/Nitrosative Cellular Stress | - |
dc.type | Article | - |
dc.identifier.doi | 10.1371/journal.pone.0073840 | - |
dc.citation.journaltitle | PLoS ONE | - |
dc.identifier.wosid | 000324695900024 | - |
dc.identifier.scopusid | 2-s2.0-84884241348 | - |
dc.citation.number | 9 | - |
dc.citation.startpage | e73840 | - |
dc.citation.volume | 8 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Karki, Rajendra | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | NITRIC-OXIDE | - |
dc.subject.keywordPlus | ADAPTER MOLECULE | - |
dc.subject.keywordPlus | FREE-RADICALS | - |
dc.subject.keywordPlus | PEROXYNITRITE | - |
dc.subject.keywordPlus | SUPEROXIDE | - |
dc.subject.keywordPlus | TLR4 | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | ANTIOXIDANT | - |
dc.subject.keywordPlus | IMMUNE | - |
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