Abstract
Sepsis, one of the leading causes of death in critically ill patients, is characterized by multiple organ dysfunction caused by dysregulated immune response to infection. Hence, we investigated that the effects of CSN6 in sepsis and the underlying mechanism. RAW264.7 cell inducted with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). CSN6 protein expression of macrophage in vitro model of sepsis was increased. We collected 10 sepsis patients and single cell analysis CSN6 expression. CSN6 aggravated inflammation of macrophage in vitro model of sepsis. CSN6 aggravated ferroptosis of macrophage in vitro model of sepsis. CSN6 aggravated mitochondrial damage of macrophage in vitro model of sepsis. CSN6 induced MIF expression of macrophage in vitro model of sepsis. MIF inhibitor reduced the effects of CSN6 on inflammation and ferroptosis of macrophage in vitro model of sepsis. CSN6 protein at 11-ARG, 21-ARG, 31-LEU, 32-ASP linked MIF protein at 280-ASN, 366-SER.In conclusion, CSN6 aggravates inflammation and myocardial injury in macrophage of sepsis by MIF signaling, suggesting that targeting this mechanism of CSN6 may be a feasible strategy to anti-inflammation for sepsis or sepsis-induced myocardial injury.