Effect of Histone Deacetylase HDAC3 on Cytokines IL-18, IL-12 and TNF-α in Patients with Intrahepatic Cholestasis of Pregnancy

Shao, Yina; Chen, Jing; Zheng, Jiao; Liu, Cai-Ru

doi:10.1159/000478958

Cited by 22 publications

(15 citation statements)

References 22 publications

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“…It has previously been reported that the accumulation of toxic BAs in hepatocytes leads to the overexpression of proinflammatory cytokines, thereby triggering liver inflammation, and promoting the development and progression of cholestasis (Yang et al, 2019). Inflammatory factors, including TNF-a, IL-6, and IL-12 can be upregulated by the activation of NF-kB, leading to aberrant leukocyte infiltration and inflammation in EIC patients (Zhang et al, 2016;Shao et al, 2017). Moreover, damage to mitochondria and the endoplasmic reticulum (ER) was observed in placenta with increased inflammatory cytokines including IL-1b, TNF-a, and regulating NF-kB pathway possesses protective effects in EIC rats (Han et al, 2018;.…”

Section: Discussionmentioning

confidence: 99%

Baicalin Protects Against 17α-Ethinylestradiol-Induced Cholestasis via the Sirtuin 1/Hepatic Nuclear Receptor-1α/Farnesoid X Receptor Pathway

Yang

Xiang

et al. 2020

Front. Pharmacol.

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Estrogen-induced cholestasis (EIC) is characterized by impairment of bile flow and accumulated bile acids (BAs) in the liver, always along with the liver damage. Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in EIC remains to be elucidated. In this study, we demonstrated that baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum biomarkers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic BAs. In addition, baicalin protected against estrogen-induced liver injury by up-regulation of the expression of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat, Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-a, IL-1b, IL-6, and NF-kB. Finally, we confirmed that baicalin maintains hepatic BA homeostasis and alleviates inflammation through sirtuin 1 (Sirt1)/hepatic nuclear receptor-1a (HNF-1a)/ farnesoid X receptor (FXR) signaling pathway. Thus, baicalin protects against estrogeninduced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1a/FXR signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Baicalin Protects Against 17α-Ethinylestradiol-Induced Cholestasis via the Sirtuin 1/Hepatic Nuclear Receptor-1α/Farnesoid X Receptor Pathway

Yang

Xiang

et al. 2020

Front. Pharmacol.

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“…The mechanism by which ICP elevates the risk of SGA infants remains obscure. Several casecontrol studies showed that the levels of proinflammatory cytokines and chemokines in placenta and maternal serum were significantly higher in the cholestasis group as compared to the control group [31,32]. Reports in vivo and in vitro found that bile acids stimulated the expression of a series of inflammatory cytokines and chemokines via activating both signal 1 and 2 of the NLRP3 inflammasome and NF-κB pathway [33,34].…”

Section: Discussionmentioning

confidence: 99%

Elevated total bile acid levels during late pregnancy are associated with the risk of small-for-gestational-age infants

Chen

Qin

et al. 2019

Preprint

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Background Intrahepatic cholestasis of pregnancy (ICP) is common in pregnant women and is diagnosed by detecting serum total bile acid (TBA) levels. We aimed to investigate the association between serum total bile acid (TBA) levels during late pregnancy and the incidence of small-for-gestational-age (SGA) infants in a Chinese population.Methods The present study was a retrospective cohort study that included 11811 eligible mother-and-singleton-offspring pairs. The correlations between TBA levels and birth sizes, including birth weight, birth length, head circumference and chest circumference, were explored. The relative risk (RR) with 95%CI for SGA infants were estimated among subjects with ICP by multiple logistic regression analysis.Results Serum TBA levels were inversely linked with birth sizes. According to TBA levels, 11120 pregnant women were controls, 563 mild ICP, and 128 severe ICP. Birth sizes in ICP groups were lower than control group, and were the lowest in severe ICP group. Further analysis showed that 24.51% neonates were SGA infants among subjects with mild ICP (adjusted RR: 3.44; 95%CI: 2.72, 4.34) and 39.06% among subjects with severe ICP (adjusted RR: 6.54; 95%CI: 4.27, 10.02), higher than 7.39% among controls. For adjusted models, linear regression analysis showed that each 1μmol/L increase in TBA levels was associated with 11.1g (95%CI: -12.7, -9.5) decrease in birth weight, 0.045cm (95%CI: -0.053, -0.036) decrease in birth length, 0.034cm (95%CI: -0.040, -0.028) decrease in head circumference, and 0.041cm (95%CI: -0.047, -0.034) decrease in chest circumference, respectively.Conclusion Elevated TBA levels during late pregnancy are associated with an increased risk of SGA infants.

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“…Epigenetics and obesity are increasingly valued by modern research [ 28 , 29 ]. The deacetylation of histone via Sirt1 was considered an important mechanism in diseases related to inflammation [ 30 ], which could regulate the expression of NF- κ B [ 31 ] and TNF- α [ 32 ]. In this trial, we noticed that high-fat diet enhanced the acetylation status of H3K9 in WAT which was reduced after EA or Resveratrol administration.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture: A Feasible Sirt1 Promoter Which Modulates Metainflammation in Diet‐Induced Obesity Rats

Luo

Liu

Liang

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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It is generally accepted that metainflammation, a state of chronic and low-grade inflammation in obesity, plays a great role in metabolic disorder like insulin resistance. To gain further insight into the mechanism of metainflammation and find feasible therapy of obesity, diet-induced obesity (DIO) rats model and Electroacupuncture (EA) treatment were established in this trail. The results indicated that rising Lee's index, hyperlipidemia, insulin resistance, and increasing inflammation factors including NF-κB, TNF-α, and Macrophages 1 were determined in DIO rats while EA is exhibiting an effective intervention. Furthermore, to clarify this phenomenon and provide new recognition of alternative medicine for the treatment of metainflammation, we found that EA activating Sirt1 and Sirt1-dependent deacetylation of histone (H3K9) was the key of modulation. It should be noted that, while possible, the activating of Sirt1 could lead to deacetylation of NF-κB also. In this study, the deacetylation of NF-κB depended on higher level of Sirt1 than H3K9, which suggested that the deacetylation via Sirt1 in metainflammation could be specific and programmed.

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Effect of Histone Deacetylase HDAC3 on Cytokines IL-18, IL-12 and TNF-α in Patients with Intrahepatic Cholestasis of Pregnancy

Cited by 22 publications

References 22 publications

Baicalin Protects Against 17α-Ethinylestradiol-Induced Cholestasis via the Sirtuin 1/Hepatic Nuclear Receptor-1α/Farnesoid X Receptor Pathway

Baicalin Protects Against 17α-Ethinylestradiol-Induced Cholestasis via the Sirtuin 1/Hepatic Nuclear Receptor-1α/Farnesoid X Receptor Pathway

Elevated total bile acid levels during late pregnancy are associated with the risk of small-for-gestational-age infants

Electroacupuncture: A Feasible Sirt1 Promoter Which Modulates Metainflammation in Diet‐Induced Obesity Rats

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