NLRP3 Inflammasome and IL-33: Novel Players in Sterile Liver Inflammation

Neumann, Katrin; Schiller, Birgit; Tiegs, Gisa

doi:10.3390/ijms19092732

Cited by 54 publications

(44 citation statements)

References 200 publications

(253 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent study has shown that hepatic inflammation and fibrogenesis are closely associated with hepatocellular necrosis and apoptosis (Lee & Friedman, ). Consistently, it has been well‐documented that danger signals such as high‐mobility group box‐1 and IL‐33 released from dying cells are critical activators in sterile inflammation that enhances the severity of several liver diseases (Gaskell, Ge, & Nieto, ; Neumann, Schiller, & Tiegs, ). Furthermore, proinflammatory cytokines such as IL‐1β and TNF‐α are closely associated with the progression of ALI because antagonizing these cytokines ameliorates the severity of liver damages induced by CCl 4 exposure (Sato et al, ; Zhu et al, ).…”

Section: Discussionmentioning

confidence: 76%

Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin‐mediated acute and chronic liver injury in mice

Kim

Yang

Jeong

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

Acute liver injury (ALI) is a life‐threatening clinical syndrome. Long‐lasting liver injury can lead to chronic hepatic inflammation and fibrogenic responses. Zerumbone (ZER), the main constituent of rhizomes of Zingiber zerumbet Smith, has a variety of functions including anticancer activity. We investigated the role of ZER on the progression of hepatotoxin‐induced liver injury. Single or repeated injection of CCl4 was used to induce acute or chronic liver injury, respectively. Mice were orally administered with ZER (10, 50 mg/kg) during the experimental period. Histopathologic analysis and serum biochemical levels revealed that ZER had hepatoprotective activities against ALI. Similar effects of ZER on injured livers were confirmed by analyses of inflammation and apoptosis‐related genes. Western blot analysis showed that protein levels of apoptotic molecules were decreased, whereas antiapoptotic protein levels were conversely increased in injured livers treated with ZER. Furthermore, chronic liver injury and its associated fibrogenesis in mice were reduced by ZER treatment. These findings from our in vivo experiments further indicate that ZER could alleviate hepatocellular toxicity and inhibit activation of primary hepatic stellate cells. Our results suggest that ZER might have potential as a safe and prophylactic alternative to prevent acute and chronic liver injury.

show abstract

Section: Discussionmentioning

confidence: 76%

Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin‐mediated acute and chronic liver injury in mice

Kim

Yang

Jeong

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…Broadly speaking, tissue damage occurs as a result of (1) sterile injury caused by a mechanical trauma or surgery (e.g. bone fracture, organ transplant or stroke), (2) pathogenic infection (including bacterial, viral, fungal or parasitic pathogens) or (3) exposure to environmental toxicant (such as cigarette smoke or asbestos) or unbalanced diet (e.g. alcohol‐induced steatohepatitis or nonalcoholic fatty liver disease) .…”

Section: Introductionmentioning

confidence: 99%

Neutrophil–macrophage cooperation and its impact on tissue repair

Bouchery

Harris

2019

Immunol Cell Biol

View full text Add to dashboard Cite

Immune cells are rapidly recruited to a site of injury or infection. Although the importance of phagocytic immune cells in clearing bacteria has long been appreciated, the advent of technologies allowing more in‐depth analysis of cellular function, such as intravital microscopy and the use of genetically modified animal models, has allowed much deeper insight into the complex roles of these cells play during tissue repair. Many immune cells contribute to the repair process; however, this review will concentrate on the involvement of the phagocytes, namely macrophages and neutrophils, with a particular focus on our more recent understanding of how interactions between these two cell types impact on the final outcome of tissue repair.

show abstract

“…Furthermore, the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway has been proposed to be involved in the maturation of IL-33. (50) Thus far, no evidence supports the activation of the NLRP3 inflammasome in AIH. It appears that both the NLRP3 inflammasome and the IL-33 pathway can become activated in sterile inflammation-associated liver diseases; therefore, components of this inflammatory pathway represent promising new therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

“…This relationship between IL‐21 and IL‐33 is also expected in the pathogenesis of AIH. Furthermore, the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway has been proposed to be involved in the maturation of IL‐33 . Thus far, no evidence supports the activation of the NLRP3 inflammasome in AIH.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin‐33/ST2‐Mediated Inflammation Plays a Critical Role in the Pathogenesis and Severity of Type I Autoimmune Hepatitis

Abe¹,

Takahashi²,

Fujita³

et al. 2019

Hepatol Commun

View full text Add to dashboard Cite

Interleukin (IL)‐33 was recently described as a new member of the IL‐1 family; members of this family have proinflammatory activity. IL‐33 and its soluble receptor ST2 (sST2) have been implicated in the pathogenesis of autoimmune diseases. This study investigated serum IL‐33 and sST2 in type I autoimmune hepatitis (AIH) and the relationship of these molecules with clinical and pathologic parameters. Subjects included 65 patients with AIH who were diagnosed in our hospital. The control population included 17 healthy individuals and 36 patients with primary biliary cholangitis (PBC). Mean age at AIH diagnosis was 55.5 years, and the male‐to‐female ratio was 6:59. Serum IL‐33 and sST2 levels were significantly higher in patients with AIH than in those with PBC or controls. Importantly, immunohistochemistry revealed high IL‐33 expression in liver sections from patients with AIH. In particular, serum IL‐33 and sST2 levels were significantly higher in acute‐onset AIH than in chronic‐onset AIH. Serum IL‐33 levels were positively correlated with serum total bilirubin (TB), alanine aminotransferase (ALT), and necroinflammatory activity in AIH. We performed multivariate logistic regression analysis and found serum IL‐33 levels to be independent factors for severe activity. Serum sST2 levels were positively correlated with serum TB and ALT and negatively correlated with serum albumin and prothrombin time in AIH. In particular, serum sST2 levels were significantly higher in severe symptoms of AIH. Serum IL‐33 and sST2 levels in patients with AIH responsive to treatment with prednisolone were significantly decreased after treatment. Interestingly, serum IL‐33 level was associated with a significantly increased risk of relapse. Conclusion: IL‐33/ST2 may play an important role in the pathogenesis and severity of AIH and may be a promising target for AIH therapy.

show abstract

NLRP3 Inflammasome and IL-33: Novel Players in Sterile Liver Inflammation

Cited by 54 publications

References 200 publications

Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin‐mediated acute and chronic liver injury in mice

Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin‐mediated acute and chronic liver injury in mice

Neutrophil–macrophage cooperation and its impact on tissue repair

Interleukin‐33/ST2‐Mediated Inflammation Plays a Critical Role in the Pathogenesis and Severity of Type I Autoimmune Hepatitis

Contact Info

Product

Resources

About