Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis

Sternak, Magdalena; Jakubowski, Andrzej; Czarnowska, E.; Słomińska, Ewa M.; Smolenski, Ryszard T.; Szafarz, Małgorzata; Walczak, Maria; Sitek, Barbara; Wójcik, Tomasz; Jasztal, Agnieszka; Kamiński, Karol; Chłopicki, Stefan

doi:10.1016/j.intimp.2015.04.053

Cited by 21 publications

(10 citation statements)

References 36 publications

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“…IL-6 is a multifunctional cytokine, which is best known for its role in the liver acute phase response. IL-6 can promote hepatocellular carcinoma (HCC) growth and metastasis via antagonism of TNF-α and IL-1β immune response (44, 45). It contributes to the development of autoimmunity disease via activating Th17 cells and inhibiting the Treg cells function.…”

Section: Discussionmentioning

confidence: 99%

Abnormal Expression of ERα in Cholangiocytes of Patients With Primary Biliary Cholangitis Mediated Intrahepatic Bile Duct Inflammation

et al. 2019

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ERα, one of the classical receptors of estrogen, has been found to be abnormally up-regulated in patients with primary biliary cholangitis (PBC), which is an important factor leading to ductopenia. ERα-mediated signaling pathways are involved in proliferation of human intrahepatic biliary epithelial cells (HiBECs) and portal inflammation. Our previous studies have shown that the expression levels of ERα in the liver tissues of PBC patients are positively correlated with the levels of serum pro-inflammatory cytokines. The present study was designed to assess the relationship between abnormal ERα expression in small bile ducts and the progression of PBC. We examined the levels of multiple cytokines and analyzed their relationship with clinical parameters of livers functions in a cohort of 43 PBC patients and 45 healthy controls (HC). The levels of ERα expression and the relation with the levels of cytokines were further assessed. The localization of cytokines and ERα-mediated signaling pathways in liver were examined using immunohistochemistry. The possible underlying mechanisms of these alterations in PBC were explored in vitro. Our results demonstrated that the levels of IL-6, IL-8, and TNF-α were increased in PBC patients, and positively correlated with the serum AKP levels and ERα expression levels. Moreover, the expression of these cytokines were up-regulated in HiBECs that were stimulated with 17β-estradiol and PPT (an ERα agonist) and they also were positive in intrahepatic bile duct of PBC patients. The ERα-mediated expression of pro-inflammatory cytokines was induced by JNK, P38, and STAT3 phosphorylation in HiBECs. In addition, the CD54 expression was increased in HiBECs after ERα activation, which induced peripheral blood monouclear cells (PBMCs) recruitment. In conclusion, the present study highlighted a key role of abnormal ERα expression in inducing an inflammatory phenotype of HiBECs, which was critical in the development of inflammation and damage in small bile duct.

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Section: Discussionmentioning

confidence: 99%

Abnormal Expression of ERα in Cholangiocytes of Patients With Primary Biliary Cholangitis Mediated Intrahepatic Bile Duct Inflammation

et al. 2019

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“…NNMT catalyzes N-methylation of NAM by transferring a methyl group from SAM to NAM and generating SAH and MNA, thus lowering the levels of SAM available for methylation reactions of histones [35, 36]. The observed reduction in H3K9me2 levels by PMS may be correlated with the enhancement of NNMT activity because elevation of NAD + /NADH was positively associated with the activity of NNMT [37]. Moreover, NAM is a precursor for NAD + biosynthesis through a salvage pathway.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells

Mao

et al. 2017

Cell Physiol Biochem

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Background: Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT) decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the role of NNMT in nickel-induced histone methylation remains unclear. Methods: BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl₂) for 72 h or 200 μM NiCl₂ for different time periods. Histone H3 on lysine 9 (H3K9) mono-, di-, and trimethylation and NNMT protein levels were measured by western blot analysis. Expressions of NNMT mRNA and the H3k9me2-associated genes, mitogen-activated protein kinase 3 (MAP2K3) and dickkopf1 (DKK1), were determined by qPCR analysis. The cellular ratio of nicotinamide adenine dinucleotide (NAD⁺) to reduced NAD (NADH) and SAM/SAH ratio were determined. Results: Exposure of BEAS-2B cells to nickel increased H3K9 dimethylation (H3K9me2), suppressed the expressions of H3K9me2-associated genes (MAP2K3 and DKK1), and induced NNMT repression at both the protein and mRNA levels. Furthermore, over-expression of NNMT inhibited nickel-induced H3K9me2 and altered the cellular SAM/SAH ratio. Additionally, the NADH oxidant phenazine methosulfate (PMS) not only reversed the nickel-induced reduction in NAD⁺/NADH but also inhibited the increase in H3K9me2. Conclusions: These findings indicate that the repression of NNMT may underlie nickel-induced H3K9 dimethylation by altering the cellular SAM/SAH ratio.

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“…The activated lymphocytes cause the release of pro-inflammatory mediators (e.g. INFγ, TNFα, IL-4), disruption of the endothelium and hepatocyte damage [10, 26, 27]. Our study, performed 24 h after ConA administration, allowed observing coagulative and haemorrhagic necrosis, inflammatory infiltration in the blood vessel walls and liver parenchyma as well as elevated levels of biochemical markers.…”

Section: Discussionmentioning

confidence: 99%

MRI-based assessment of liver perfusion and hepatocyte injury in the murine model of acute hepatitis

Byk

Jasiński

Bartel

et al. 2016

Magn Reson Mater Phy

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ObjectiveTo assess alterations in perfusion and liver function in the concanavalin A (ConA)-induced mouse model of acute liver failure (ALF) using two magnetic resonance imaging (MRI)-based methods: dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA contrast agent and arterial spin labelling (ASL).Materials and methodsBALB/c mice were studied using a 9.4 T MRI system. The IntraGateFLASHTM and FAIR-EPI pulse sequences were used for optimum mouse abdomen imaging.ResultsThe average perfusion values for the liver of the control and ConA group were equal to 245 ± 20 and 200 ± 32 ml/min/100 g (p = 0.008, respectively). DCE-MRI showed that the time to the peak of the image enhancement was 6.14 ± 1.07 min and 9.72 ± 1.69 min in the control and ConA group (p < 0.001, respectively), while the rate of the contrast wash-out in the control and ConA group was 0.037 ± 0.008 and 0.021 ± 0.008 min−1 (p = 0.004, respectively). These results were consistent with hepatocyte injury in the ConA-treated mice as confirmed by histopathological staining.ConclusionsBoth the ASL and DCE-MRI techniques represent a reliable methodology to assess alterations in liver perfusion and hepatocyte integrity in murine hepatitis.

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Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis

Cited by 21 publications

References 36 publications

Abnormal Expression of ERα in Cholangiocytes of Patients With Primary Biliary Cholangitis Mediated Intrahepatic Bile Duct Inflammation

Abnormal Expression of ERα in Cholangiocytes of Patients With Primary Biliary Cholangitis Mediated Intrahepatic Bile Duct Inflammation

Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells

MRI-based assessment of liver perfusion and hepatocyte injury in the murine model of acute hepatitis

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