Kaerophyllin inhibits hepatic stellate cell activation by apoptotic bodies from hepatocytes

Lee, Ting-Fang; Lin, Yun‐Lian; Huang, Yi-Tsau

doi:10.1111/j.1478-3231.2011.02485.x

Cited by 17 publications

(16 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of NF-κB is linked to phosphorylation and proteolytic degradation of IκBα [16]. TNF-α is known as one of the strongest stimuli of NF-κB activity [23]. Indeed, we found that TNF-α induced phosphorylation of IκBα level in LX-2 cells compared with the normal group and the phosphorylation of IκBα was further induced in LX-2 cells pretreated with NLRC5-siRNA, whereas NLRC5-siRNA notably reduce cell survival.…”

Section: Discussionmentioning

confidence: 85%

NLRC5 Mediates IL-6 and IL-1β Secretion in LX-2 Cells and Modulated by the NF-κB/Smad3 Pathway

Huang

et al. 2015

Inflammation

View full text Add to dashboard Cite

Recent data have shown that nucleotide-binding domain leucine-rich repeat proteins (NLRs), a class of innate immune receptors that respond to pathogen attack or cellular stress, have gained increasing attention. NLRC5 (NLR family, CARD domain containing 5) is the largest member of the NLR family, which has recently been identified as a critical regulator of immune responses. Until recently, the function of NLRC5 has been a matter of debate. In this study, we explore the role of NLRC5 in cytokine secretion and the role of the nuclear factor-κB (NF-κB) signaling pathway in tumor necrosis factor-alpha (TNF-α)-induced NLRC5 expression in LX-2 cells. We demonstrated that overexpression of NLRC5 results in an upregulation of IL-6 and IL-1β secretion. On the other hand, knockdown of NLRC5 by transfecting siRNA decreased IL-6 and IL-1β secretion in LX-2 cells. Meanwhile, the results showed that pyrrolidine dithiocarbamate (PDTC) (a specific inhibitor of the NF-κB signaling pathway) inhibited NLRC5 expression and NLRC5 silencing could increase the expression levels of p65 in cell nucleus accompanied with upregulated phosphorylation of Smad3 protein levels in response to TNF-α. These results indicated that NLRC5 plays a significant role in TNF-α-enhanced cytokine (IL-6 and IL-1β) secretion of LX-2 cells and the NF-κB/Smad3 signal pathway is involved in its induction of expression.

show abstract

Section: Discussionmentioning

confidence: 85%

NLRC5 Mediates IL-6 and IL-1β Secretion in LX-2 Cells and Modulated by the NF-κB/Smad3 Pathway

Huang

et al. 2015

Inflammation

View full text Add to dashboard Cite

show abstract

“…24-well plates were added reporter lysis buffer (100 µl/well), and 20 µl cell lysate mixed with 100 µl luciferin in white 96-well plates. Luminescence was detected by luminometer-VICTOR2 Multilabel Counter (Perkin Elmer Inc., Waltham, MA, USA), as previously reported by us [27], [28].…”

Section: Methodsmentioning

confidence: 99%

“…HSC-T6 cells were seeded on collagen coated 24-well plates [28], [30], [31] at a density of 9×10 4 cells/well. After 24 hr serum starvation, a monolayer of cells was scratched by a 200 µl tip in serum-free medium.…”

Section: Methodsmentioning

confidence: 99%

Inhibitory Effect of Tanshinone IIA on Rat Hepatic Stellate Cells

Liu¹,

Huang

2014

PLoS ONE

Self Cite

View full text Add to dashboard Cite

BackgroundAnti-inflammation via inhibition of NF-κB pathways in hepatic stellate cells (HSCs) is one therapeutic approach to hepatic fibrosis. Tanshinone IIA (C19H18O3, Tan IIA) is a lipophilic diterpene isolated from Salvia miltiorrhiza Bunge, with reported anti-inflammatory activity. We tested whether Tan IIA could inhibit HSC activation.Materials and MethodsThe cell line of rat hepatic stellate cells (HSC-T6) was stimulated with lipopolysaccharide (LPS) (100 ng/ml). Cytotoxicity was assessed by MTT assay. HSC-T6 cells were pretreated with Tan IIA (1, 3 and 10 µM), then induced by LPS (100 ng/ml). NF-κB activity was evaluated by the luciferase reporter gene assay. Western blotting analysis was performed to measure NF-κB-p65, and phosphorylations of MAPKs (ERK, JNK, p38). Cell chemotaxis was assessed by both wound-healing assay and trans-well invasion assay. Quantitative real-time PCR was used to detect gene expression in HSC-T6 cells.ResultsAll concentrations of drugs showed no cytotoxicity against HSC-T6 cells. LPS stimulated NF-κB luciferase activities, nuclear translocation of NF-κB-p65, and phosphorylations of ERK, JNK and p38, all of which were suppressed by Tan IIA. In addition, Tan IIA significantly inhibited LPS-induced HSCs chemotaxis, in both wound-healing and trans-well invasion assays. Moreover, Tan IIA attenuated LPS-induced mRNA expressions of CCL2, CCL3, CCL5, IL-1β, TNF-α, IL-6, ICAM-1, iNOS, and α-SMA in HSC-T6 cells.ConclusionOur results demonstrated that Tan IIA decreased LPS-induced HSC activation.

show abstract

“…Isolation of kaerophyllin from BS is described as previously reported [11]. The structure of kaerophyllin was identified by their spectroscopic method and comparison with the literature values [13,14].…”

Section: Methodsmentioning

confidence: 99%

“…Kaerophyllin did not affect hepatocyte viability. Using MTT assays, rat hepatocytes showed no cytotoxicity in the presence of kaerophyllin up to 60 μ m for 48 h [11].…”

Section: Methodsmentioning

confidence: 99%

Protective effects of kaerophyllin against liver fibrogenesis in rats

Lee¹,

Lin²,

Huang³

2011

Eur J Clin Investigation

Self Cite

View full text Add to dashboard Cite

show abstract

Kaerophyllin inhibits hepatic stellate cell activation by apoptotic bodies from hepatocytes

Abstract: Kaerophyllin inhibited AB-induced LX-2 activation and migration with downregulation of Akt/ERK phosphorylations and NF-κB activity. Our study suggests a novel platform for screening anti-fibrotic compounds with ABs.

Cited by 17 publications

References 41 publications

NLRC5 Mediates IL-6 and IL-1β Secretion in LX-2 Cells and Modulated by the NF-κB/Smad3 Pathway

NLRC5 Mediates IL-6 and IL-1β Secretion in LX-2 Cells and Modulated by the NF-κB/Smad3 Pathway

Inhibitory Effect of Tanshinone IIA on Rat Hepatic Stellate Cells

Protective effects of kaerophyllin against liver fibrogenesis in rats

Contact Info

Product

Resources

About