2006
DOI: 10.1016/j.bbrc.2006.10.102 View full text |Buy / Rent full text
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Abstract: Sepsis induced lethality is characterized by amplified host innate immune response. Nrf2, a bZIP transcription factor, regulates a battery of cellular antioxidative genes and maintains cellular redox homeostasis. This study demonstrates that increasing Nrf2 activity by a potent small molecule activator, CDDO-Im (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole), protects from deregulation of lipopolysaccharide (LPS) induced innate immune response. In response to LPS stimuli, nrf2-deficient (nrf2 -/-)… Show more

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“…The reciprocal regulation between Nrf2 system function and PTEN expression has been suggested by several studies [34,40] . In this study, by using an Nrf2 inhibitor, we found that Nrf2 is causally involved in the effect of metformin on the regulation of PTEN and insulin signaling (Supplementary Figure 3).…”
Section: Discussionmentioning
“…This Nrf2-mediated transcriptional interference appears to be independent of the level of reactive oxygen species. Although the conventional hypothesis is that Nrf2 alleviates inflammation as a secondary consequence of its antireactive oxygen species and anti-oxidation function (25), these results suggest that Nrf2 inhibits the induction of pro-inflammatory cytokine gene transcription. Thus, Nrf2 appears to be the key regulator of two important cytoprotective pathways, anti-inflammation and anti-oxidation.…”
Section: Anti-inflammation By Nrf2mentioning
“…In vivo, DMF treatment of experimental autoimmune encephalomyelitis (EAE) was also associated with a Th2 bias, which may be a consequence of induction of antigen-presenting antiinflammatory type II dendritic cells (DCs) (11). Consistent with these observations, results indicate Nrf2 itself may regulate innate and adaptive T-cell immune responses in models of organ-specific inflammation (12,13), including EAE (14,15). Nevertheless, although DMF demonstrated prominent reduction of inflammatory measures of MS (8,9), it is not clear that this benefit is mediated through activation of Nrf2.…”
mentioning
“…Also in Nrf2-deficient mouse embryonic fibroblasts exposed to both inflammatory cytokines INF-␥ and TNF-␣, we observed that the Keap1/Nrf2/ARE pathway is essential for the anti-inflammatory effects of triterpenoids (19). Others have reported that Nrf2 deficiency also resulted in augmented lung inflammation in response to nonlethal challenge with LPS or TNF-␣, suggesting that Nrf2 suppressed inflammation by inhibiting NF-B activation through regulation of redox balance (35), and that activation of Nrf2-dependent compensatory antioxidative pathways by a triterpenoid (CDDO-Im) protects from LPS-induced inflammatory response and mortality (36). Very recently, hepatocyte-specific conditional Keap1 knockout and nrf2-WT mice, but not nrf2-knockout mice, pretreated with CDDO-Im were found to be highly resistant to Con A-mediated inflammatory liver injury (37).…”
Section: Discussionmentioning
“…Thioglycollate-elicited peritoneal macrophages were isolated from mice using methods described previously (16,19).…”
Section: Peritoneal Macrophagesmentioning