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Sesquiterpene lactones inhibit advanced oxidation protein product-induced MCP-1 expression in podocytes via an IKK/NF-κB-dependent mechanism.

Zhao Y, Chen SJ, Wang JC, Niu HX, Jia QQ, Chen XW, Du XY, Lu L, Huang B, Zhang Q, Chen Y, Long HB - Oxid Med Cell Longev (2015)

Bottom Line: Sesquiterpene lactones (SLs), originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN.The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression.Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβ and NF-κB p65 phosphorylation and IκBα degradation.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China ; Department of Nephrology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, Hubei 441021, China.

ABSTRACT
Inflammation is a relevant factor in the pathogenesis of diabetes nephropathy (DN). Sesquiterpene lactones (SLs), originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN. To determine whether advanced oxidation protein products (AOPPs) can induce the expression of chemokine monocyte chemoattractant protein- (MCP-) 1 in cultured mouse podocytes and to explore the mechanisms of the potential renoprotection of SLs, we treated podocytes with AOPPs and SLs (parthenolide and its derivatives micheliolide, compound 1, and compound 2). MCP-1 mRNA and protein expression were tested using quantitative real-time PCR and ELISA, respectively, and the protein levels of IKKβ, phospho-IKKβ, IκBα, NF-κB p65, phospho-NF-κB p65, and tubulin were analyzed by Western blotting. AOPPs activated the expression of MCP-1 mRNA and protein in a dose- and time-dependent manner, activated IKKβ and NF-κB p65, and promoted IκBα degradation. The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression. Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβ and NF-κB p65 phosphorylation and IκBα degradation. Taken together, these findings provide a novel explanation for the anti-inflammatory effects of SLs that will ultimately benefit DN and potentially other inflammatory and immune renal diseases.

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Related in: MedlinePlus

Structures of natural SLs and synthetic derivatives.
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fig1: Structures of natural SLs and synthetic derivatives.

Mentions: Conditionally immortalized mouse podocytes were generously provided by Shankland et al. (Harvard Medical School, Charlestown, MA, USA) and cultured as previously described [32]. Briefly, undifferentiated podocytes were grown in RPMI 1640 containing 10% FBS (BRL Co. Ltd., USA), penicillin (100 U/mL), streptomycin (100 mg/mL), and 50 IU/mL recombinant murine IFN-γ (Pepro Tech, USA) at 33°C (permissive conditions). To acquire a differentiated phenotype, podocytes were cultured at 37°C in the absence of IFN-γ (nonpermissive conditions) for 10–14 days. Differentiated podocytes were starved in RPMI 1640 for 24 h and then treated with various reagents. Podocytes between passages 10 and 20 were used in all experiments. PTL and MCL were purchased from Accendatech Co., Ltd (Tianjin, China), compound 1 and compound 2 were synthesized following the procedure provided in [33, 34] by Accendatech Co., Ltd (Tianjin, China), and the purity of those four compounds was more than 98% (Figure 1). Depending on the experiment demands, podocytes were divided into different groups and then treated with the drugs or/and AOPPs.


Sesquiterpene lactones inhibit advanced oxidation protein product-induced MCP-1 expression in podocytes via an IKK/NF-κB-dependent mechanism.

Zhao Y, Chen SJ, Wang JC, Niu HX, Jia QQ, Chen XW, Du XY, Lu L, Huang B, Zhang Q, Chen Y, Long HB - Oxid Med Cell Longev (2015)

Structures of natural SLs and synthetic derivatives.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4309307&req=5

fig1: Structures of natural SLs and synthetic derivatives.
Mentions: Conditionally immortalized mouse podocytes were generously provided by Shankland et al. (Harvard Medical School, Charlestown, MA, USA) and cultured as previously described [32]. Briefly, undifferentiated podocytes were grown in RPMI 1640 containing 10% FBS (BRL Co. Ltd., USA), penicillin (100 U/mL), streptomycin (100 mg/mL), and 50 IU/mL recombinant murine IFN-γ (Pepro Tech, USA) at 33°C (permissive conditions). To acquire a differentiated phenotype, podocytes were cultured at 37°C in the absence of IFN-γ (nonpermissive conditions) for 10–14 days. Differentiated podocytes were starved in RPMI 1640 for 24 h and then treated with various reagents. Podocytes between passages 10 and 20 were used in all experiments. PTL and MCL were purchased from Accendatech Co., Ltd (Tianjin, China), compound 1 and compound 2 were synthesized following the procedure provided in [33, 34] by Accendatech Co., Ltd (Tianjin, China), and the purity of those four compounds was more than 98% (Figure 1). Depending on the experiment demands, podocytes were divided into different groups and then treated with the drugs or/and AOPPs.

Bottom Line: Sesquiterpene lactones (SLs), originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN.The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression.Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβ and NF-κB p65 phosphorylation and IκBα degradation.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China ; Department of Nephrology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, Hubei 441021, China.

ABSTRACT
Inflammation is a relevant factor in the pathogenesis of diabetes nephropathy (DN). Sesquiterpene lactones (SLs), originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN. To determine whether advanced oxidation protein products (AOPPs) can induce the expression of chemokine monocyte chemoattractant protein- (MCP-) 1 in cultured mouse podocytes and to explore the mechanisms of the potential renoprotection of SLs, we treated podocytes with AOPPs and SLs (parthenolide and its derivatives micheliolide, compound 1, and compound 2). MCP-1 mRNA and protein expression were tested using quantitative real-time PCR and ELISA, respectively, and the protein levels of IKKβ, phospho-IKKβ, IκBα, NF-κB p65, phospho-NF-κB p65, and tubulin were analyzed by Western blotting. AOPPs activated the expression of MCP-1 mRNA and protein in a dose- and time-dependent manner, activated IKKβ and NF-κB p65, and promoted IκBα degradation. The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression. Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβ and NF-κB p65 phosphorylation and IκBα degradation. Taken together, these findings provide a novel explanation for the anti-inflammatory effects of SLs that will ultimately benefit DN and potentially other inflammatory and immune renal diseases.

Show MeSH
Related in: MedlinePlus