IL-33 exacerbates liver sterile inflammation by amplifying neutrophil extracellular trap formation

Yazdani, Hamza O.; Chen, Hui‐Wei; Tohme, Samer; Tai, Sheng; Windt, Dirk J. van der; Loughran, Patricia; Rosborough, Brian R.; Sud, Vikas; Beer‐Stolz, Donna; Turnquist, Hēth; Tsung, Allan; Huang, Hai

doi:10.1016/j.jhep.2017.09.010

Cited by 93 publications

(100 citation statements)

References 42 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings argue against acute formation of NETs after reperfusion. A previous study has suggested evidence for NET formation induced by ischemia/reperfusion injury in humans, (3) but this study only demonstrated elevated MPO-DNA complex levels in samples taken on postoperative day 1 without directly linking these elevated levels to ischemia/reperfusion injury.…”

Section: To the Editorcontrasting

confidence: 78%

Reply

Meijenfeldt

Lisman

2019

Liver Transpl

View full text Add to dashboard Cite

Section: To the Editorcontrasting

confidence: 78%

Reply

Meijenfeldt

Lisman

2019

Liver Transpl

View full text Add to dashboard Cite

“…In addition, ST2 blockade completely ameliorated neutrophilia in IFNγ −/− Prf1 −/− mice (Figure H). We hypothesize that this is due to reduced CD8+ T cell activation, which we know is needed for neutrophilia; yet it is also known that IL‐33 signaling can act directly on neutrophils to exacerbate inflammation . Overall, these data show that IFNγ is not necessary for development of a CD8‐driven HLH‐like disease in a novel murine model.…”

Section: Resultsmentioning

confidence: 79%

Genetic Deficiency of Interferon‐γ Reveals Interferon‐γ–Independent Manifestations of Murine Hemophagocytic Lymphohistiocytosis

Burn

Weaver

Rood

et al. 2019

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective. Familial hemophagocytic lymphohistiocytosis (FHLH) is a complex cytokine storm syndrome caused by genetic abnormalities rendering CD8+ T cells and natural killer cells incapable of cytolytic killing. In murine models of FHLH, interferon-γ (IFNγ) produced by CD8+ T cells has been identified as a critical mediator of disease, and an IFNγ-blocking antibody (emapalumab) has recently been approved by the Food and Drug Administration. However, development of hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) in patients who are genetically unresponsive to IFNγ questions the absolute necessity of IFNγ in driving disease. This study was undertaken to determine the necessity of IFNγ in driving HLH.Methods. IFNγ −/− Prf1 −/− mice were infected with lymphocytic choriomeningitis virus (LCMV), and HLH immunopathologic features, including survival, weight loss, cytopenias, cytokine profiles, and immune cell phenotypes, were assessed. Mixed bone marrow chimeras were created to determine the immune cell-intrinsic role of IFNγ receptor signaling. CD8+ T cell depletion and interleukin-33 (IL-33)/ST2 blockade were performed using monoclonal antibodies.Results. LCMV infection of IFNγ −/− Prf1 −/− mice resulted in severe HLH-like disease. CD8+ T cells and the IL-33/ ST2 axis remained essential mediators of disease; however, IFNγ-independent HLH immunopathology correlated with a 10-15-fold increase in neutrophilia (P < 0.001) and an altered cytokine milieu dominated by IL-6, IL-1β, and granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.05). Furthermore, IFNγ regulated CD8+ T cell expression of GM-CSF and neutrophil survival.Conclusion. IFNγ is not necessary for the development of fulminant HLH, requiring physicians to consider caseby-case treatment strategies. Use of therapies that target upstream activators of CD8+ T cells, such as IL-33/ST2 signaling, may be more universally applicable treatment options that ameliorate both IFNγ-dependent and -independent manifestations of HLH/MAS.

show abstract

“…Hepatic ischemia-reperfusion (I/R) injury is a complication of hepatic surgery, and it can arise after liver resection and transplantation [1,2]. Hepatic I/R injury induces oxidative stress, inflammation, and other disorders in the liver, thus leading to the liver damage in patients requiring liver surgery [3][4][5][6]. However, the mechanisms underlying the I/R injury are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways

Guo

Zhang

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Hepatic ischemia-reperfusion (I/R) injury is a serious complication in patients who have undergone hepatic surgery such as orthotopic liver transplantation and partial hepatectomy. Recently, a new cytoprotective agent, ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), was reported to protect against hepatic I/R injury. However, the protective mechanism of UDCA-LPE is not fully understood. Therefore, we conducted this study to explore its underlying mechanism. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the liver lipid metabolism changes in mice during I/R. KEGG enrichment indicated that UDCA-LPE is likely to exert its protective role by regulating fatty acid (FA) metabolism. Further analysis found that UDCA-LPE significantly increased the ratio of oleic acid (OA) to palmitic acid (PA). We found that mice pretreated with OA improved tolerance to hepatic I/R injury. In addition, the phosphorylation level of AKT was markedly upregulated during oxidative stress to promote p65 nuclear translocation, triggering an inflammatory response that exacerbated cell damage and OA treatment significantly inhibited this process. Notably, OA was found to inhibit H2O2-induced oxidative stress, inflammation, and cell death in HepG2 cells. Furthermore, we found that OA supplementation to the medium did not result in a significant increase in intracellular OA, but marked increase in the ratio of OA to PA, which may be an important mechanism for the inflammatory response induced by oxidative stress during I/R. Finally, we demonstrated that OA increased the level of autophagy in HepG2 cells, which may be one of the protective mechanisms against oxidative stress. Collectively, this study revealed that FA metabolism functionally determines the oxidative stress-related inflammation caused by hepatic I/R. We hypothesize that OA treatment may be a promising strategy for preventing and treating I/R-induced liver damage.

show abstract

IL-33 exacerbates liver sterile inflammation by amplifying neutrophil extracellular trap formation

Cited by 93 publications

References 42 publications

Reply

Reply

Genetic Deficiency of Interferon‐γ Reveals Interferon‐γ–Independent Manifestations of Murine Hemophagocytic Lymphohistiocytosis

Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways

Contact Info

Product

Resources

About