Sepsis is a challenging clinical syndrome caused by a dysregulated host response to infection. Here, we identified an unexpected proseptic activity of aconitate decarboxylase 1 (ACOD1) in monocytes and macrophages. Previous studies have suggested that ACOD1, also known as immune-responsive gene 1,...
摘要 The immune response gene 1 (IRG1) and its metabolite itaconate are implicated in modulating inflammation and oxidative stress, with potential relevance to sepsis-induced myocardial dysfunction (SIMD). This study investigates their roles in SIMD using both in vivo and in vitro models. Mice were...
Sepsis is a serious, potentially fatal disease caused by the body's reaction to microbial invasions by bacteria, viruses, and fungi. Current research shows that the process of fighting sepsis passes through two phases. The first phase is a cytokine storm, and the second phase involves a cycle...
et al. IRG1 induced by heme oxygenase-1/carbon monoxide inhibits LPS-mediated sepsis and pro-inflammatory cytokine production. Cell Mol. Immunol. 13, 170–179 (2016). CAS PubMed Google Scholar Kane, M. J. et al. Altered gene expression in cultured microglia in response to simulated blast...
In the mouse sepsis syndrome model, Keap1 deletion in macrophages resulted in reduced levels of inflammatory mediators, organ injury, bacteremia and mortality, whereas Nrf2 deletion had the opposite effects27. We found that KEAP1 plays an important role in macrophage pro-inflammatory activity through...
, MYD88 directly blocks autophagic degradation of STING1 and causes subsequentIRF3/JUN-mediated ACOD1 gene transcription. Consequently, the conditional deletion of STING1 in myeloid cells fails to produce ACOD1 and itaconate, thereby protecting mice against endotoxemia and polymicrobial sepsis. ...
Intriguingly, itaconate accumulation has been shown to correlate with immune paralysis, as found for example in sepsis30. Citraconate derivatives may thus prove beneficial in the treatment of patients with end-stage sepsis or other scenarios characterized by exhaustion of innate immunity. In addition,...
Aconitate decarboxylase 1 (ACOD1) Sepsis Inflammation Metabolism Disease Introduction The innate immune system is comprised of different components, including various immune cells (e.g., macrophages, monocytes, dendritic cells [DCs], and neutrophils), which can rapidly recognize invading pathogens throug...
Sepsis is one of the oldest and most elusive syndromes in medicine that is defined by a dysregulated host response to pathogen infection (Singer et al., 2016). Monocytes and macrophages are the main sources of the production of immune mediators in septic shock, which can be activated by patho...
SepsisInflammationMetabolismDiseaseImmunometabolism is a dynamic process involving the interplay of metabolism and immune response in health and diseases. Increasing evidence suggests that impaired immunometabolism contributes to infectious and inflammatory diseases. In particular, the mitochondrial enzyme aconitate...