Interleukin-17 is involved in α-naphthylisothiocyanate-induced liver injury in mice

Kobayashi, Masanori; Higuchi, Satonori; Mizuno, Keita; Tsuneyama, Koichi; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

doi:10.1016/j.tox.2010.05.011

Cited by 40 publications

(16 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…). In previous studies by our group (Kobayashi et al , ; Higuchi et al , ), we confirmed that the expression levels of mRNA and protein were similar for interleukins and chemokines. Thus, changes in mRNA were mainly followed in the present study, except for IL‐4.…”

Section: Resultssupporting

confidence: 88%

“…We recently reported that IL‐17 is involved in halothane‐ and α ‐naphthylisothiocyanate‐induced acute liver injury in mice (Kobayashi et al , , ) and that IL‐4 is involved in dicloxacillin‐induced acute liver injury in mice (Higuchi et al , ). In this study, we found that Th2 cytokine‐mediated immune responses play a role in MTZ‐induced acute liver injury in mice.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Th2 cytokine‐mediated methimazole‐induced acute liver injury in mice

Kobayashi

Higuchi

Ide³

et al. 2012

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical practice. The pathogenesis of DILI usually involves the participation of the parent drug or metabolites that either affect cellular function or elicit an immune response. However, the mechanisms leading to DILI are unknown in most cases. Methimazole (MTZ) is used as an antithyroid drug and is well known to have induced liver injuries such as cholestatic hepatitis in a small number of human cases. Immune-mediated reactions were also suggested to play a role in MTZ-induced acute liver injury, but the mechanism underlying this process has not been elucidated. To address this issue, we measured plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, hepatic glutathione levels, hepatic expression of CD4⁺ Th cell-related transcriptional factors, cytokines and chemokines, plasma interleukin (IL)-4 levels and histopathological changes in the liver following MTZ (450 mg kg⁻¹ , p.o.) administration in mice. The hepatic expression of mRNA for Th2 cell-related factors, such as GATA-binding protein, macrophage inflammatory protein-2 (MIP-2) and plasma IL-4 levels, as well as plasma AST and ALT levels, was significantly increased in mice treated with MTZ. These changes were markedly enhanced by pre-treatment with L-buthionine sulfoximine (3 mmol kg⁻¹, i.p.) and MTZ (15 mg kg⁻¹, p.o.). Neutralization of IL-4 using a monoclonal anti-mouse IL-4 antibody (100 µg/mouse, single i.p.) suppressed the hepatotoxic effect of MTZ. In conclusion, this report is the first to demonstrate that Th2 cytokine-mediated immune responses are involved in MTZ-induced acute liver injury in mice.

show abstract

Section: Resultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Th2 cytokine‐mediated methimazole‐induced acute liver injury in mice

Kobayashi

Higuchi

Ide³

et al. 2012

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, it has been proved that ANIT inhibited the expressions of bile acid transporters in mouse primary hepatocytes (Guo et al, 2014). In the liver, ANIT also significantly decreased the expressions of Mrp2 (multidrug resistance-associated protein 2), FXR (farnesoid X receptor), Ntcp (Na + -dependent taurocholate cotransporter), Bsep (bile salt export pump), and CYP7A1 (cholesterol 7α-hydroxylase) (Wang T. et al, 2014), and it has been reported that ANIT made bile duct epithelial cells produce substance which was regarded as an activator for neutrophils to hurt hepatocytes (Hill and Roth, 1998; Kobayashi et al, 2010). The lipid peroxidation caused by reactive oxygen species (ROS) was also related to the development of the liver injury that was induced by ANIT in mice (Kongo et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model

Liu

Yuan

et al. 2017

Front. Pharmacol.

View full text Add to dashboard Cite

Intrahepatic cholestasis is a kind of clinical syndrome along with hepatotoxicity which caused by intrahepatic and systemic accumulations of bile acid. There are several crucial generating factors of the pathogenesis of cholestasis, such as inflammation, dysregulation of bile acid transporters and oxidative stress. SIRT1 is regarded as a class III histone deacetylase (HDAC). According to a set of researches, SIRT1 is one of the most important factors which can regulate the hepatic bile acid metabolism. SRT1720 is a kind of activator of SIRT1 which is 1000 times more potent than resveratrol, and this paper is aimed to study its protective influence on hepatotoxicity and cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in mice. The findings revealed that SRT1720 treatment increased FXR and Nrf2 gene expressions to shield against hepatotoxicity and cholestasis induced by ANIT. The mRNA levels of hepatic bile acid transporters were also altered by SRT1720. Furthermore, SRT1720 enhanced the antioxidative system by increasing Nrf2, SOD, GCLc, GCLm, Nqo1, and HO-1 gene expressions. In conclusion, a protective influence could be provided by SRT1720 to cure ANIT-induced hepatotoxicity and cholestasis, which was partly through FXR and Nrf2 activations. These results indicated that SIRT1 could be regarded as a therapeutic target to cure the cholestasis.

show abstract

“…The IL‐17 axis has also been linked to hepatic injury: an increased frequency of IL‐17A‐expressing cells (and increased IL‐17A expression) in diverse human liver diseases and mouse models of liver injury . Further, IL‐17A neutralization or genetic deletion of IL‐17A has been shown to be protective in mouse models of acute hepatitis, drug‐induced liver injury, and lipopolysaccharide (LPS)‐induced liver injury during high‐fat diet stress . IL‐17RA is widely expressed in the liver and IL‐17 drives neutrophil chemokine expression by such cells .…”

mentioning

confidence: 99%

IL‐17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice

et al. 2014

View full text Add to dashboard Cite

Inflammation plays a central pathogenic role in the pernicious metabolic and end organ sequelae of obesity. Among these sequelae, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the developed world. The twinned observations that obesity is associated with increased activation of the IL-17 axis and that this axis can regulate liver damage in diverse contexts prompted us to address the role of IL-17RA signaling in the progression of NAFLD. We further examined whether microbe-driven IL-17A regulated NAFLD development and progression. We show here that IL-17RA−/− mice respond to high fat diet stress with significantly greater weight gain, visceral adiposity and hepatic steatosis than wild type controls. However, obesity-driven lipid accumulation was uncoupled from its end organ consequences in IL-17RA−/− mice, which exhibited decreased steatohepatitis, NADPH-oxidase enzyme expression and hepatocellular damage. Neutralization of IL-17A significantly reduced obesity-driven hepatocellular damage in wild type mice. Further, colonization of mice with segmented filamentous bacteria (SFB), a commensal that induces IL-17A production, exacerbated obesity-induced hepatocellular damage. In contrast, SFB depletion protected from obesity-induced hepatocellular damage. Conclusion These data indicate that obesity-driven activation of the IL-17 axis is central to the development and progression of NAFLD to steatohepatitis and identify the IL-17 pathway as a novel therapeutic target in this condition.

show abstract

Interleukin-17 is involved in α-naphthylisothiocyanate-induced liver injury in mice

Cited by 40 publications

References 17 publications

Th2 cytokine‐mediated methimazole‐induced acute liver injury in mice

Th2 cytokine‐mediated methimazole‐induced acute liver injury in mice

SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model

IL‐17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice

Contact Info

Product

Resources

About