ArticlePloS one2017
Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- MULTIMODAL NUCLEAR FACTOR-ERYTHROID-2-RELATED FACTOR (NRF2) THERAPY IN THE CONTEXT OF MAMMALIAN TARGET OF RAPAMYCIN (MTOR) INHIBITION REPROGRAMS THE ACUTE SYSTEMIC AND PULMONARY IMMUNE RESPONSE AFTER COMBINED BURN AND INHALATION INJURY.Shock (Augusta, Ga.) · 2024Article
- Triterpenoid CDDO-EA inhibits lipopolysaccharide-induced inflammatory responses in skeletal muscle cells through suppression of NF-κB.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Characterization of the Basal and mTOR-Dependent Acute Pulmonary and Systemic Immune Response in a Murine Model of Combined Burn and Inhalation Injury.International journal of molecular sciences · 2022Article
- Plasma extracellular vesicles released after severe burn injury modulate macrophage phenotype and function.Journal of leukocyte biology · 2022Article
- Burn Injury Induces Proinflammatory Plasma Extracellular Vesicles That Associate with Length of Hospital Stay in Women: CRP and SAA1 as Potential Prognostic Indicators.International journal of molecular sciences · 2021Article
- Macrophage immunomodulation through new polymers that recapitulate functional effects of itaconate as a power house of innate immunity.Advanced functional materials · 2021Article
- Article
- Targeting Cytokine Release Through the Differential Modulation of Nrf2 and NF-κB Pathways by Electrophilic/Non-Electrophilic Compounds.Frontiers in pharmacology · 2020Article
- Sex-Based Differences in Inpatient Burn Mortality.World journal of surgery · 2019Article
- One-hit wonder: Late after burn injury, granulocytes can clear one bacterial infection but cannot control a subsequent infection.Burns : journal of the International Society for Burn Injuries · 2019Article
- The role of nuclear factor erythroid-2-related factor 2 expression in radiocontrast-induced nephropathy.Scientific reports · 2019Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0-48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) agonist, CDDO-Me(bardoxolone methyl), reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10) secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl) also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA). Hence, our findings with CDDO-Me(bardoxolone methyl) and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells.
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