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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

AOPPs stimulation increased the expression of MCP-1 in cultured podocytes. Podocytes were incubated with the indicated concentration of AOPPs for 24 h or 200 μg/mL of AOPPs for the indicated time and subjected to MCP-1 mRNA and protein expression analysis. AOPP treatment increased the expression of MCP-1 at both the mRNA (c, d) and protein levels (a, b) in a dose- and time-dependent manner. Data are expressed as the means ± SD of three independent experiments. ANOVA, *P < 0.05, **P < 0.01, and ***P < 0.001 versus CON. CON, untreated cells; MSA, mouse serum albumin.
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fig2: AOPPs stimulation increased the expression of MCP-1 in cultured podocytes. Podocytes were incubated with the indicated concentration of AOPPs for 24 h or 200 μg/mL of AOPPs for the indicated time and subjected to MCP-1 mRNA and protein expression analysis. AOPP treatment increased the expression of MCP-1 at both the mRNA (c, d) and protein levels (a, b) in a dose- and time-dependent manner. Data are expressed as the means ± SD of three independent experiments. ANOVA, *P < 0.05, **P < 0.01, and ***P < 0.001 versus CON. CON, untreated cells; MSA, mouse serum albumin.

Mentions: To investigate whether AOPPs induce the expression of MCP-1 in podocytes, we tested the expression levels of MCP-1 mRNA by qPCR and MCP-1 protein by ELISA. The data showed that AOPPs can promote the expression of MCP-1 protein in a dose-dependent manner and reach a maximum level at a concentration of 200 μg/mL. At the same time, AOPPs can enhance the expression of MCP-1 protein in a time-dependent manner, and a significant increase in MCP-1 protein was observed after a 24 h incubation. qPCR revealed that AOPPs significantly increased the expression of MCP-1 and peaked at 200 μg/mL at 24 h. The expression of MCP-1 was unchanged in cells incubated with native MSA or medium alone, suggesting that the upregulation of MCP-1 was associated with an oxidative modification of MSA (Figure 2).


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)

AOPPs stimulation increased the expression of MCP-1 in cultured podocytes. Podocytes were incubated with the indicated concentration of AOPPs for 24 h or 200 μg/mL of AOPPs for the indicated time and subjected to MCP-1 mRNA and protein expression analysis. AOPP treatment increased the expression of MCP-1 at both the mRNA (c, d) and protein levels (a, b) in a dose- and time-dependent manner. Data are expressed as the means ± SD of three independent experiments. ANOVA, *P < 0.05, **P < 0.01, and ***P < 0.001 versus CON. CON, untreated cells; MSA, mouse serum albumin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: AOPPs stimulation increased the expression of MCP-1 in cultured podocytes. Podocytes were incubated with the indicated concentration of AOPPs for 24 h or 200 μg/mL of AOPPs for the indicated time and subjected to MCP-1 mRNA and protein expression analysis. AOPP treatment increased the expression of MCP-1 at both the mRNA (c, d) and protein levels (a, b) in a dose- and time-dependent manner. Data are expressed as the means ± SD of three independent experiments. ANOVA, *P < 0.05, **P < 0.01, and ***P < 0.001 versus CON. CON, untreated cells; MSA, mouse serum albumin.
Mentions: To investigate whether AOPPs induce the expression of MCP-1 in podocytes, we tested the expression levels of MCP-1 mRNA by qPCR and MCP-1 protein by ELISA. The data showed that AOPPs can promote the expression of MCP-1 protein in a dose-dependent manner and reach a maximum level at a concentration of 200 μg/mL. At the same time, AOPPs can enhance the expression of MCP-1 protein in a time-dependent manner, and a significant increase in MCP-1 protein was observed after a 24 h incubation. qPCR revealed that AOPPs significantly increased the expression of MCP-1 and peaked at 200 μg/mL at 24 h. The expression of MCP-1 was unchanged in cells incubated with native MSA or medium alone, suggesting that the upregulation of MCP-1 was associated with an oxidative modification of MSA (Figure 2).

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