Modulatory effect of rhein on IL-1α-induced responses in human chondrocytes: A comparative study between antibody microarrays and specific ELISAs

Deffaud, J.; Kirchmeyer, Mélanie; Domagala, Florence; Ficheux, H.; Netter, Patrick; Bianchi, Arnaud; Jouzeau, J.-Y.

doi:10.3233/bir-2008-0484

Cited by 13 publications

(8 citation statements)

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“…EGCG alone treatment was also effective in down-regulating the basal level of expression of GRO, GRO-α, MCP-1 and MIP-1β in OA chondrocytes. Consistent with the present findings, induction of chemokines has been previously described after stimulation of chondrocytes with IL-1 [ 56 , 57 ], but their suppression by EGCG has not been previously described in OA chondrocytes. However, Ahmed et al (2006) reported similar inhibitory effects of EGCG (50 μM) on RANTES, ENA-78, GRO-α, and MCP-1 production in IL-1β-stimulated RA-synovial fibroblasts [ 58 ].…”

Section: Discussionsupporting

confidence: 93%

Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes

2011

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IntroductionEpigallocatechin-3-gallate (EGCG) is a bioactive polyphenol of green tea and exerts potent anti-inflammatory effects by inhibiting signaling events and gene expression. Interleukin-1beta (IL-1β) is the principal cytokine linked to cartilage degradation in osteoarthritis (OA). The objective of this study was to evaluate the global effect of EGCG on IL-1β-induced expression of proteins associated with OA pathogenesis in human chondrocytes.MethodsPrimary OA chondrocytes were pretreated with EGCG (10 to 100 uM) and then stimulated with IL-1β (5 ng/ml) for 24 hours. Culture supernatants were incubated with cytokine antibody arrays and immunoreactive proteins (80 proteins) were visualized by enhanced chemiluminiscence. Effect of EGCG on IL-1β-induced expression of 18 selected genes was verified by Real time-PCR and effect on IL-6, IL-8 and tumor necrosis factor-alpha (TNF-α) production was determined using specific ELISAs. Western immunoblotting was used to analyze the effect of EGCG on the interleukin-1 receptor-associated kinase 1 (IRAK-1) and TNF receptor-associated factor 6 (TRAF-6) proteins in IL-1β-stimulated chondrocytes. The role of nuclear factor kappa-B (NF-κB) and mitogen activated protein kinases (MAPKs) in the regulation of selected genes and the mechanism involved in EGCG mediated modulation of these genes was determined by using specific inhibitors for NF- κB (MG132) and MAPKs (p38-MAPK, SB202190; JNK-MAPK, SP600125, ERK-MAPK, PD98059).ResultsOut of 80 proteins present on the array, constitutive expression of 14% proteins was altered by EGCG treatment. No significant stimulatory effect was observed on the proteins associated with cartilage anabolic response. Stimulation with IL-1β enhanced the expression of 29 proteins. Expression of all 29 proteins up-regulated by IL-1β was found to be suppressed by EGCG. EGCG also inhibited the expression of the signaling intermediate TRAF-6 at 50 and 100 uM concentrations (P < 0.05). Our results identified several new targets of EGCG, including epithelial neutrophil activating peptide-78 (ENA-78), granulocyte macrophage colony stimulation factor (GM-CSF), growth- related oncogene (GRO), GRO-α, IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), MCP-3, macrophage inflammatory protein-1beta (MIP-1β), granulocyte chemotactic protein-2 (GCP-2), MIP-3alpha, interferon-gamma-inducible protein-10 (IP-10), nucleosome assembly protein-2 (NAP-2) and leukemia inhibitory factor (LIF). The inhibitory effects of EGCG were mainly mediated by inhibiting the activation of NF-κB and c-Jun N-terminal Kinase (JNK)-MAPK in human chondrocytes.ConclusionsOur results suggest that the potential of EGCG in OA treatment/prevention may be related to its ability to globally suppress the inflammatory response in human chondrocytes. These results identify additional new targets of EGCG and advocate that EGCG may be a potent chondroprotective agent in OA.

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Section: Discussionsupporting

confidence: 93%

Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes

2011

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“…In extrinsic pathway, the levels of Fas and its ligand are enhanced by the induced apoptosis effect of rhein (Kuo et al, 2004 ; Ip et al, 2007 ). The specific ELISA experiment demonstrated that rhein can increase the production of sTNFR I and sTNFR II (Deffaud et al, 2008 ). Some studies reported that the expression of ligand TNF-α is inhibited by rhein (Heo et al, 2010 ; Meng et al, 2015 ; Yu et al, 2015 ).…”

Section: Rhein Regulation On Cellular Processesmentioning

confidence: 99%

A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient

et al. 2016

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Rhein is a major medicinal ingredient isolated from several traditional Chinese medicines, including Rheum palmatum L., Aloe barbadensis Miller, Cassia angustifolia Vahl., and Polygonum multiflorum Thunb. Rhein has various pharmacological activities, such as anti-inflammatory, antitumor, antioxidant, antifibrosis, hepatoprotective, and nephroprotective activities. Although more than 100 articles in PubMed are involved in the pharmacological mechanism of action of rhein, only a few focus on the relationship of crosstalk among multiple pharmacological mechanisms. The mechanism of rhein involves multiple pathways which contain close interactions. From the overall perspective, the pathways which are related to the targets of rhein, are initiated by the membrane receptor. Then, MAPK and PI3K-AKT parallel signaling pathways are activated, and several downstream pathways are affected, thereby eventually regulating cell cycle and apoptosis. The therapeutic effect of rhein, as a multitarget molecule, is the synergistic and comprehensive result of the involvement of multiple pathways rather than the blocking or activation of a single signaling pathway. We review the pharmacological mechanisms of action of rhein by consulting literature published in the last 100 years in PubMed. We then summarize these pharmacological mechanisms from a comprehensive, interactive, and crosstalk perspective. In general, the molecular mechanism of action of drug must be understood from a systematic and holistic perspective, which can provide a theoretical basis for precise treatment and rational drug use.

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“…Rhein markedly decreased IL-1 converting enzyme protein production [ 3 ] and partially increased tissue inhibitor of metalloproteinase-1 (TIMP-1) synthesis and NO production of IL-1 β [ 22 , 23 ]. Moreover, rhein slightly decreased monocyte chemotactic protein-1 (MCP-1) production, while it increased the levels of IL-1 receptor antagonist (IL-1RA), cytokine receptors IL-6R, soluble tumor necrosis factor (sTNF) R I and R II, and some chemokines or intercellular adhesion molecule (ICAM)-1 in IL-1 (1 ng/mL)-stimulated chondrocytes from osteoarthritic patients [ 24 ]. Rhein (5–20 mg/mL) inhibited 1,25(OH) 2 D 3 -induced osteocalcin release, urokinase plasminogen activator (u-PA) production, and plasminogen activator inhibitor (PAI)-1 levels but increased the levels of insulin-like growth factor-1, prostaglandin E 2, and cyclooxygenase-2 in human OA primary subchondral osteoblasts [ 25 ].…”

Section: Pharmacologymentioning

confidence: 99%

Rhein: A Review of Pharmacological Activities

Zhou

Xia

Yue

et al. 2015

Evidence-Based Complementary and Alternative Medicine

150

114

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Rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid) is a lipophilic anthraquinone extensively found in medicinal herbs, such as Rheum palmatum L., Cassia tora L., Polygonum multiflorum Thunb., and Aloe barbadensis Miller, which have been used medicinally in China for more than 1,000 years. Its biological activities related to human health are being explored actively. Emerging evidence suggests that rhein has many pharmacological effects, including hepatoprotective, nephroprotective, anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. The present review provides a comprehensive summary and analysis of the pharmacological properties of rhein, supporting the potential uses of rhein as a medicinal agent.

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Modulatory effect of rhein on IL-1α-induced responses in human chondrocytes: A comparative study between antibody microarrays and specific ELISAs

Cited by 13 publications

References 53 publications

Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes

Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes

A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient

Rhein: A Review of Pharmacological Activities

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