Autophagy in macrophages regulates the inflammasome and protects against liver injury

Ding, Wen–Xing; Jaeschke, Hartmut

doi:10.1016/j.jhep.2015.10.003

Cited by 24 publications

(14 citation statements)

References 21 publications

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“…However, within that percentage of total extra-hepatic macrophages, 5.75% were BMC-derived in the transplanted fibrotic group. Depending on the stimulus, macrophages can be polarized in M1, with pro-inflammatory profile and release of cytokines such TNF-α, IL-1β, IL-12 and reactive oxygen species (ROS) or M2, anti-inflammatory and immuno-suppressive profile with release of cytokines such as IL-10, IL-14 and IL-13 [ 29 , 30 , 31 ]. Extrahepatic macrophages derived from circulating monocytes are attracted to injured sites and extend the damage with pro-inflammatory and pro-fibrotic actions (profile M1) as seen in the fibrotic groups through cytokine profiling.…”

Section: Discussionmentioning

confidence: 99%

Cytokines, hepatic cell profiling and cell interactions during bone marrow cell therapy for liver fibrosis in cholestatic mice

et al. 2017

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Bone marrow cells (BMC) migrate to the injured liver after transplantation, contributing to regeneration through multiple pathways, but mechanisms involved are unclear. This work aimed to study BMC migration, characterize cytokine profile, cell populations and proliferation in mice with liver fibrosis transplanted with GFP+ BMC. Confocal microscopy analysis showed GFP+ BMC near regions expressing HGF and SDF-1 in the fibrotic liver. Impaired liver cell proliferation in fibrotic groups was restored after BMC transplantation. Regarding total cell populations, there was a significant reduction in CD68+ cells and increased Ly6G+ cells in transplanted fibrotic group. BMC contributed to the total populations of CD144, CD11b and Ly6G cells in the fibrotic liver, related to an increment of anti-fibrotic cytokines (IL-10, IL-13, IFN-γ and HGF) and reduction of pro-inflammatory cytokines (IL-17A and IL-6). Therefore, HGF and SDF-1 may represent important chemoattractants for transplanted BMC in the injured liver, where these cells can give rise to populations of extrahepatic macrophages, neutrophils and endothelial progenitor cells that can interact synergistically with other liver cells towards the modulation of an anti-fibrotic cytokine profile promoting the onset of liver regeneration.

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Section: Discussionmentioning

confidence: 99%

Cytokines, hepatic cell profiling and cell interactions during bone marrow cell therapy for liver fibrosis in cholestatic mice

et al. 2017

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“…It is a catabolic lysosomal process that degrades cytoplasmic materials including misfolded proteins and damaged organelles as a cellular response and survival mechanism in reaction to an assortment of stress conditions. (1) Controlled by the products of autophagy-related genes (Atg), autophagy occurs under normal physiological conditions but is regulated by several factors, including cytokines such as interferon-gamma, tumor necrosis factor-alpha (TNF-α; up-regulation), as well as interleukin-4 (IL-4) and IL-13 (down-regulation). Inhibition of autophagy in macrophages by knockdown of Atg7 or Atg16L1 promotes IL-1β secretion in response to lipopolysaccharide (LPS).…”

Section: See Article On Page 595mentioning

confidence: 99%

Hepatocyte Autophagy: Maintaining a Toxic‐Free Environment

Francis

Alpini

et al. 2020

Hepatology

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“…Upon sensing noxious signals, NLRP3 recruits pro-caspase-1 and the adaptor molecule ASC (apoptotic specklike protein-containing CARD), resulting in activation of caspase-1 as well as secretion of IL-1β and interleukin-18 (IL-18), which play a critical role in promoting liver inflammation ( 19 ). NLRP3 inflammasome can be activated by a variety of danger sensors, such as excess ATP, uric acid, and mitochondrion DNA, while mitochondria-derived reactive oxygen species (mtROS) was considered as a major activator ( 20 – 23 ). Interestingly, a study recently illustrated that Concanavalin A (ConA)-induced hepatitis was accompanied with reactive oxygen species (ROS) production ( 24 ).…”

Section: Introductionmentioning

confidence: 99%

NOD-Like Receptor Protein 3 Inflammasome-Dependent IL-1β Accelerated ConA-Induced Hepatitis

et al. 2018

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Autoimmune hepatitis (AIH) is a progressive inflammatory disorders of unknown etiology, characterized by immune-mediated destruction of hepatocytes and massive production of cytokines. Interleukin-1β is a pleiotropic proinflammatory cytokine and well known to be critical in a variety of autoimmune diseases. However, the role of interleukin-1β (IL-1β) in AIH is still indistinct. Here, we first investigated the significance of NOD-like receptor protein 3 (NLRP3) inflammasome-dependent IL-1β in the pathogenesis of AIH with a murine model of immune-mediated hepatitis induced by Concanavalin A (ConA). In ConA-treated mice, pathogenic elevated NLRP3, Cleaved caspase-1 and IL-1β levels, as well as an inflammatory cell death known as pyroptosis predominantly occurred in the livers. Strikingly, NLRP3−/− and caspase-1−/− mice were broadly protected from hepatitis as determined by decreased histological liver injury, serum aminotransferase (ALT)/aspartate transaminase levels, and pyroptosis. In vivo intervention with recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) strongly suppressed ConA-induced hepatitis by decreasing tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) secretion, and inflammatory cell infiltration into livers. Additionally, rhIL-1Ra-pretreated mice developed significantly reduced NLRP3 inflammasome activation and reactive oxygen species (ROS) generation. Scavenging of ROS by N-acetyl-cysteine also attenuated NLRP3 inflammasome activation and liver inflammation, indicating that the essential role of ROS in mediating NLRP3 inflammasome activation in ConA-induced hepatitis. In conclusion, our results demonstrated that NLRP3 inflammasome-dependent IL-1β production was crucial in the pathogenesis of ConA-induced hepatitis, which shed light on the development of promising therapeutic strategies for AIH by blocking NLRP3 inflammasome and IL-1β.

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Autophagy in macrophages regulates the inflammasome and protects against liver injury

Cited by 24 publications

References 21 publications

Cytokines, hepatic cell profiling and cell interactions during bone marrow cell therapy for liver fibrosis in cholestatic mice

Cytokines, hepatic cell profiling and cell interactions during bone marrow cell therapy for liver fibrosis in cholestatic mice

Hepatocyte Autophagy: Maintaining a Toxic‐Free Environment

NOD-Like Receptor Protein 3 Inflammasome-Dependent IL-1β Accelerated ConA-Induced Hepatitis

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