Sex hormone affects the severity of non-alcoholic steatohepatitis through the MyD88-dependent IL-6 signaling pathway

Xin, Guangda; Qin, Shaoyou; Wang, Song; Wang, Xu; Zhang, Yonggui; Wang, Jiangbin

doi:10.1177/1535370215570189

Cited by 23 publications

(19 citation statements)

References 39 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…S4). The levels that we recorded were similar to those previously published by others for male (testosterone) and female (estradiol) mice (22,23). Our results do not support obvious hormonal modifications as a mechanism by which gestational BPA increases EAE susceptibility in adult male mice.…”

Section: Gestational Bpa Exposure Alters Responses Of Macrophages Culsupporting

confidence: 79%

Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model of multiple sclerosis

Rogers

Mishra

Hahn

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Environmental and hormonal factors are implicated in dysimmunity in multiple sclerosis. We investigated whether bisphenol-A, a prominent contaminant with endocrine-disrupting capabilities, altered susceptibility in an inflammatory model of multiple sclerosis. We found that gestational, but not adult, exposure to bisphenol-A increased the development of experimental autoimmune encephalomyelitis in adulthood in male, but not female, mice when a suboptimal disease-inducing immunization was used. Gestational bisphenol-A in male mice primed macrophages in adulthood and raised granulocyte-colony stimulating factor and neutrophil counts/activity postsuboptimal immunization. Neutralizing granulocyte-colony stimulating factor blocked susceptibility to disease in bisphenol-A mice. Early life exposure to bisphenol-A may represent an environmental consideration in multiple sclerosis.

show abstract

Section: Gestational Bpa Exposure Alters Responses Of Macrophages Culsupporting

confidence: 79%

Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model of multiple sclerosis

Rogers

Mishra

Hahn

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Splenic artery resistive index (index of organ damage) overlapped between patients with NASH and those with fatty livers, but showed a difference to controls, pointing out that NASH patients did not present increased liver injury (followed by fibrosis and eventual portal hypertension) compared to fatty liver patients [29]. With regards to IL-6, most interestingly, recent results showed that different sex hormone-related interventions affected the severity of NASH, likely by impacting on the level of sex hormones and modulating the Toll-Like Receptor-MyD88-IL-6 signalling pathway, clearly reinforcing the hypothesis that IL-6 plays a key role in worsening the simpler fatty liver disease [30]. Finally, in a large, multi-ethnic population with NAFLD, IL-6 was independently associated with the prevalence and severity of subclinical atherosclerosis [31].…”

Section: Spleenmentioning

confidence: 68%

Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy

Tarantino

Citro

Capone

2019

JCM

114

110

View full text Add to dashboard Cite

Focusing on previously published mechanisms of non-alcoholic fatty liver disease (NAFLD), their uncertainty does not always permit a clear elucidation of the grassroot alterations that are at the basis of the wide-spread illness, and thus curing it is still a challenge. There is somehow exceptional progress, but many controversies persist in NAFLD research and clinical investigation. It is likely that hidden mechanisms will be brought to light in the near future. Hereby, the authors present, with some criticism, classical mechanisms that stand at the basis of NAFLD, and consider contextually different emerging processes. Without ascertaining these complex interactions, investigators have a long way left ahead before finding an effective therapy for NAFLD beyond diet and exercise. few are conclusively accepted by experts. We try to provide evidence of the complexity, and for some aspects the contradictions, of the main lines of basic and clinical research addressing this topic. The Role of Reactive Oxygen Species (ROS) OverproductionMalnutrition splits in two directions; undernutrition and overnutrition; both of them leading to severe health complications: Famine and overweight/obesity are the result of calorie deficit or excess, and both of them are major health problems. Constantly eating excess calories leads body fat stores to expand. One of the most active and productive hypotheses about the mechanisms inducing or worsening obesity and consequently NAFLD is the over-production of reactive oxygen species (ROS). Oxidative stress accompanying obesity is reckoned to be a key factor in the development of insulin resistance (IR), [4]. In fact, obese mice treated with NADPH oxidase inhibitors (reducing ROS) have clearly demonstrated the involvement of ROS in the genesis of IR, hepatic steatosis, and T2DM [5]. Mitochondria are clearly considered to be main contributors to oxidative stress in obesity induced by chronic over-nutrition, with subsequent reduced insulin sensitivity or IR [6]. The trigger that causes the oxidative stress in obesity is the energy surplus that eventually generates reducing equivalents. These exceed the rate of ATP utilization, giving space to the over-production of O 2 , and consequently reducing the redox-buffering capacity [7]. The aforementioned pathway has been fully highlighted in mice, characterized by deletion of manganese superoxide dismutase at the adipocyte level through enhanced mitochondrial biogenesis, mediated by uncoupling protein 1 [8].

show abstract

“…Plasma IL-6 values were increased in NASH patients in a pilot study [31]. Recent studies indicated that IL-6 contributed to the development of NAFLD [32,33]. IL-6 has also been demonstrated to play a pivotal role in the dichotomous differentiation programmes of Th17.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-26a–interleukin (IL)-6–IL-17 axis regulates the development of non-alcoholic fatty liver disease in a murine model

et al. 2016

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryNon-alcoholic fatty liver disease (NAFLD) is a hepatic presentation of obesity and metabolic syndrome. MicroRNA 26a (Mir-26a) has been reported to play functions in cellular differentiation, cell growth, cell apoptosis and metastasis. A recent paper indicated that Mir-26a regulated insulin sensitivity and metabolism of glucose and lipids. However, the role of Mir-26a in NAFLD still needs to be investigated further. In our current study, vectors encoding pre-Mir-26a (LV-26a) and an empty lentiviral vector (LV-Con) delivered approximately 2 3 10 7 transforming units of recombinant lentivirus were injected into mice through the tail vein. LV-26a-infected mice were protected from glucose dysmetabolism and showed markedly decreased total liver weight, hepatic triglyceride deposition and serum alanine transaminase (ALT) concentration when compared with LV-Con-treated mice. LV-26a-treated mice also exhibited decreased infiltration of immune cells in the liversomething attributed to reduce infiltration of T cell receptor (TCR)-gd 1 , granulocyte-differentiation antigen-1 (Gr-1) 1 cells and CD11b 1 cells. Next, we found that Mir-26a inhibited the expression of interleukin (IL)217 and IL-6 in vivo and in vitro. Furthermore, the decreased expression of IL-17 in the liver tissue induced by Mir-26a was abrogated completely by IL-6 overexpression. The decreased total liver weight, hepatic triglyceride deposition and serum ALT concentration induced by Mir-26a was also abrogated completely by IL-6 over-expression. In conclusion, the Mir-26a-IL-6-IL-17 axis regulates the development of NAFLD in a murine model.

show abstract

Sex hormone affects the severity of non-alcoholic steatohepatitis through the MyD88-dependent IL-6 signaling pathway

Cited by 23 publications

References 39 publications

Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model of multiple sclerosis

Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model of multiple sclerosis

Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy

MicroRNA-26a–interleukin (IL)-6–IL-17 axis regulates the development of non-alcoholic fatty liver disease in a murine model

Contact Info

Product

Resources

About