Interaction of Neutrophils with Macrophages Promotes IL-1β Maturation and Contributes to Hepatic Ischemia–Reperfusion Injury

Abstract

Accumulating evidence suggests that IL-1β plays a pivotal role in the pathophysiology of hepatic ischemia-reperfusion (I/R) injury; however, the mechanism by which I/R triggers IL-1β production in the liver remains unclear. Recent data have shown that neutrophils contribute to hepatic I/R injury independently of the inflammasomes regulating IL-1β maturation. Thus, we investigated the role of neutrophils in IL-1β maturation and tissue injury in a murine model of hepatic I/R. IL-1β was released from the I/R liver and its deficiency reduced reactive oxygen species generation, apoptosis, and inflammatory responses, such as inflammatory cell infiltration and cytokine expression, thereby resulting in reduced tissue injury. Depletion of either macrophages or neutrophils also attenuated IL-1β release and hepatic I/R injury. In vitro experiments revealed that neutrophil-derived proteinases process pro-IL-1β derived from macrophages into its mature form independently of caspase-1. Furthermore, pharmacological inhibition of serine proteases attenuated IL-1β release and hepatic I/R injury in vivo. Taken together, the interaction between neutrophils and macrophages promotes IL-1β maturation and causes IL-1β-driven inflammation in the I/R liver. Both neutrophils and macrophages are indispensable in this process. These findings suggest that neutrophil-macrophage interaction is a therapeutic target for hepatic I/R injury and may also provide new insights into the inflammasome-independent mechanism of IL-1β maturation in the liver.

Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: Potential role of ferroptosis

“…Previous investigations have demonstrated that inflammation contributes to the development of hepatic I/R injury; therefore, we performed real‐time RT‐PCR analysis to assess the expression of inflammatory cytokines and cell markers. The expression of Il1b , Il6 , Tnfa , Ccl2 , and Ly6g (neutrophil marker) was increased in the I/R liver, and this increase was significantly inhibited by Fer‐1 (Figure A).…”

“…Overnight (16 hours)‐fasted mice underwent hepatic I/R or sham operation. Partial hepatic ischemia was produced as previously described with some modifications . Briefly, mice were anesthetized with isoflurane.…”

“…Histology and immunohistochemistry were performed as described previously . The paraffin‐embedded tissue sections were stained with hematoxylin and eosin (HE).…”

Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure

“…Histology and immunohistochemistry were performed as described previously 16 . Paraffin-embedded tissue sections were stained with hematoxylin and eosin.…”

Effect of Beta-Blockade on the Expression of Regulatory MicroRNA after Severe Trauma and Chronic Stress

“…Previous studies have shown that circulating IL-1b, TNF-a, and CRP are significantly elevated early after hemorrhagic shock, hypoxia, and ischemia-reperfusion injury. [30][31][32] Elevations of circulating IL-6 occur early and have been shown to correlate with severe trauma and degree of tissue injury. 33 In addition, our analysis revealed 45 bone marrow miRs with significantly altered expression after LCHS/CS compared with those rodents that received propranolol after LCHS/CS and naïve rodents.…”