LPS mediated Nfκb activation varies between activated human hepatic stellate cells from different donors

Muehlbauer, Marcus; Thasler, WE; Schöelmerich, Juergen; Hellerbrand, Claus

doi:10.1016/s0016-5085(03)83621-1

Cited by 4 publications

(5 citation statements)

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“…The secretion of cytokines and chemokines, including TNFa, IL6, IL1b, MIP-1a, MIP-1b, and RANTES by HSCs is regulated by a variety of cell surface receptors, including pattern recognition receptors such as Toll-like receptors (TLRs). Activation of TLR-4 by lipopolysaccharide (LPS) stimulates synthesis of interferon-c, TNFa, IL6 and IL1b by both quiescent and activated HSCs [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

SHP-dependent and -independent induction of peroxisome proliferator-activated receptor-γ by the bile acid sensor farnesoid X receptor counter-regulates the pro-inflammatory phenotype of liver myofibroblasts

et al. 2011

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Section: Introductionmentioning

confidence: 99%

SHP-dependent and -independent induction of peroxisome proliferator-activated receptor-γ by the bile acid sensor farnesoid X receptor counter-regulates the pro-inflammatory phenotype of liver myofibroblasts

et al. 2011

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“…(9,12,13) Activation of TLR4 has been shown to enhance cytokine production, macrophage polarization, (14) inflammatory cell recruitment, and hepatic stellate cell (HSC) activation. (15) Pentraxin-3 (PTX3) is a member of the humoral arm of innate immunity and is involved in the modulation of inflammation and tissue remodeling. (16) Moreover, PTX3 can also act in response to pathogens by acting as a soluble pattern-recognition receptor (16) or binding to pathogens.…”

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confidence: 99%

“…TLR4 downstream signaling and cytokine production are mainly governed by myeloid differentiation primary response 88, with early activation of nuclear factor κB and production of proinflammatory cytokines, and TIR domain–containing adapter‐inducing interferon (TRIF), essential for late activation of nuclear factor κB, interferon regulatory factor 3, and production of interferon‐inducible genes . Activation of TLR4 has been shown to enhance cytokine production, macrophage polarization, inflammatory cell recruitment, and hepatic stellate cell (HSC) activation …”

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confidence: 99%

Pentraxin‐3 modulates lipopolysaccharide‐induced inflammatory response and attenuates liver injury

et al. 2017

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Acute-on-chronic liver injury is characterized by an important inflammatory response frequently associated with endotoxemia. In this context, acute phase proteins such as Pentraxin-3 (PTX3) are released, however, little is known about their role in chronic liver disease. The aim of this study was to elucidate the role of PTX3 in liver injury. Role of PTX3 was evaluated in cultured human cells, liver tissue slices and mice with acute-on-chronic liver injury. PTX3 expression was assessed in tissue and serum samples from 54 patients with alcoholic hepatitis (AH). PTX3 expression was up-regulated in animal models of liver injury and strongly induced by lipopolysaccharide (LPS). Liver cell fractionation showed that macrophages and activated hepatic stellate cells (HSC) were the main cell types expressing PTX3 in liver injury. Ex vivo, and in vivo studies showed that PTX3 treatment attenuated LPS-induced liver injury, inflammation and cell recruitment. Mechanistically, PTX3 mediated HSC wound-healing response. Moreover, PTX3 modulated LPS-induced inflammation in human primary liver macrophages and peripheral monocytes by enhancing a TRIF-dependent response and favoring a macrophage IL-10-like phenotype. Additionally, hepatic and plasma PTX3 levels were up-regulated in patients with AH, a prototypic acute-on-chronic condition and its expression correlated with disease severity scores, endotoxemia, infections and short-term mortality. Thus, suggesting that expression of PTX3 found in patients could be a counterregulatory response to injury. Conclusion Experimental and human evidences suggest that in addition to being a potential biomarker for AH, PTX3 participates in wound-healing response and attenuates LPS-induced liver injury and inflammation. Therefore, administration of PTX3 could be a promising therapeutic strategy in acute-on-chronic conditions, particularly those associated with endotoxemia.

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“…Our results demonstrated that chrysophanol decreased the viability of LPS-induced activated HSC-T6 cells by apoptosis. Mühlbauer et al reported that LPS induces HSC activation through the Toll-like receptor 4 (TLR4), the NF-κB signaling pathway, and the IL-8 activity [26]. LPS exposure increases proliferation, ROS generation, oxidative stress, and mRNA expression of Collagen-1 and α-SMA of activated HSCs [27].…”

Section: Discussionmentioning

confidence: 99%

Chrysophanol Prevents Lipopolysaccharide‐Induced Hepatic Stellate Cell Activation by Upregulating Apoptosis, Oxidative Stress, and the Unfolded Protein Response

Chiu

Cui

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Hepatic stellate cell (HSC) activation is a vital driver of liver fibrosis. Recent research efforts have emphasized the clearance of activated HSCs by apoptosis, senescence, or reversion to the quiescent state. LPS induces human HSC activation directly and contributes to liver disease progression. Chrysophanol is an anthraquinone with hepatoprotective and anti-inflammatory effects. This study aimed to investigate the pharmacological effects and mechanisms of chrysophanol in an LPS-induced activated rat HSC cell line (HSC-T6). The fibrosis phenotype was identified from the expression of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and integrin β1 by western blot analysis. We examined DNA fragmentation by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. We detected the apoptotic markers p53 and cleaved caspase-3 by western blot analysis. Intracellular ROS were labeled with 2′,7′-dichlorofluorescein diacetate (DCF-DA) and the levels were measured by flow cytometry. Finally, we evaluated the ER stress markers binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP) by Western blot analysis. Our results showed that chrysophanol decreased HSC-T6 cell viability in LPS-induced activated HSCs. Chrysophanol increased the expression of α-SMA, CTGF, integrin βI, p53, cleaved caspase-3, and DNA fragmentation. Chrysophanol also elevated ROS levels and increased the expression of BiP and CHOP. Pretreatment with chrysophanol prevented LPS-induced HSC-T6 cell activation by upregulating apoptosis, ROS accumulation, unfolded protein response (UPR) activation, and the UPR proapoptotic effect.

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LPS mediated Nfκb activation varies between activated human hepatic stellate cells from different donors

Cited by 4 publications

References 0 publications

SHP-dependent and -independent induction of peroxisome proliferator-activated receptor-γ by the bile acid sensor farnesoid X receptor counter-regulates the pro-inflammatory phenotype of liver myofibroblasts

SHP-dependent and -independent induction of peroxisome proliferator-activated receptor-γ by the bile acid sensor farnesoid X receptor counter-regulates the pro-inflammatory phenotype of liver myofibroblasts

Pentraxin‐3 modulates lipopolysaccharide‐induced inflammatory response and attenuates liver injury

Chrysophanol Prevents Lipopolysaccharide‐Induced Hepatic Stellate Cell Activation by Upregulating Apoptosis, Oxidative Stress, and the Unfolded Protein Response

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