Limits...
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.

Show MeSH

Related in: MedlinePlus

SLs decreased the AOPP-induced expression of MCP-1 protein in a dose- and time-dependent manner. Podocytes were preincubated with the indicated concentration of MCL, compound 1, or compound 2 for 1 h before treatment with 200 μg/mL of AOPPs for 24 h. PTL (5 μM) was used as a positive control (a, b, and c). Aliquots of 200 μg/mL AOPPs were used to treat podocytes for 24 h, and then MCL (5 μM), compound 1 (10 μM), or compound 1 (2.5 μM) was added for the indicated times (d, e, and f). The expression levels of MCP-1 protein were determined by ELISA. SLs decreased the AOPP-induced expression of MCP-1 protein in a dose- and time-dependent manner. The data are expressed as the means ± SEM of three independent experiments. ANOVA, ###P < 0.001 versus CON; *P < 0.05, **P < 0.01, and ***P < 0.001 versus AOPP. CON, untreated cells; MSA, mouse serum albumin.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4309307&req=5

fig4: SLs decreased the AOPP-induced expression of MCP-1 protein in a dose- and time-dependent manner. Podocytes were preincubated with the indicated concentration of MCL, compound 1, or compound 2 for 1 h before treatment with 200 μg/mL of AOPPs for 24 h. PTL (5 μM) was used as a positive control (a, b, and c). Aliquots of 200 μg/mL AOPPs were used to treat podocytes for 24 h, and then MCL (5 μM), compound 1 (10 μM), or compound 1 (2.5 μM) was added for the indicated times (d, e, and f). The expression levels of MCP-1 protein were determined by ELISA. SLs decreased the AOPP-induced expression of MCP-1 protein in a dose- and time-dependent manner. The data are expressed as the means ± SEM of three independent experiments. ANOVA, ###P < 0.001 versus CON; *P < 0.05, **P < 0.01, and ***P < 0.001 versus AOPP. CON, untreated cells; MSA, mouse serum albumin.

Mentions: Next, we tested the hypothesis that SLs (MCL, compound 1, and compound 2), as derivatives of PTL, may have the same anti-inflammatory response in podocytes. After preincubation with SLs, cells were treated with 200 μg/mL AOPPs for 24 h. PTL (5 μM) was used as a positive control. The expression of MCP-1 mRNA was determined by qPCR, and MCP-1 protein expression was measured by ELISA. The results presented in Figures 4(a), 4(b), and 4(c) and Figures 5(a), 5(b), and 5(c) demonstrated that MCL, compound 1, and compound 2 responded in a dose-dependent manner to prevent the expression of MCP-1 mRNA and protein. Additionally, MCL, compound 1, and compound 2 at a concentration of 5 μM, 10 μM, and 2.5 μM, respectively, produced an almost equal inhibitory effect on MCP-1 as 5 μM of PTL.


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)

SLs decreased the AOPP-induced expression of MCP-1 protein in a dose- and time-dependent manner. Podocytes were preincubated with the indicated concentration of MCL, compound 1, or compound 2 for 1 h before treatment with 200 μg/mL of AOPPs for 24 h. PTL (5 μM) was used as a positive control (a, b, and c). Aliquots of 200 μg/mL AOPPs were used to treat podocytes for 24 h, and then MCL (5 μM), compound 1 (10 μM), or compound 1 (2.5 μM) was added for the indicated times (d, e, and f). The expression levels of MCP-1 protein were determined by ELISA. SLs decreased the AOPP-induced expression of MCP-1 protein in a dose- and time-dependent manner. The data are expressed as the means ± SEM of three independent experiments. ANOVA, ###P < 0.001 versus CON; *P < 0.05, **P < 0.01, and ***P < 0.001 versus AOPP. CON, untreated cells; MSA, mouse serum albumin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: SLs decreased the AOPP-induced expression of MCP-1 protein in a dose- and time-dependent manner. Podocytes were preincubated with the indicated concentration of MCL, compound 1, or compound 2 for 1 h before treatment with 200 μg/mL of AOPPs for 24 h. PTL (5 μM) was used as a positive control (a, b, and c). Aliquots of 200 μg/mL AOPPs were used to treat podocytes for 24 h, and then MCL (5 μM), compound 1 (10 μM), or compound 1 (2.5 μM) was added for the indicated times (d, e, and f). The expression levels of MCP-1 protein were determined by ELISA. SLs decreased the AOPP-induced expression of MCP-1 protein in a dose- and time-dependent manner. The data are expressed as the means ± SEM of three independent experiments. ANOVA, ###P < 0.001 versus CON; *P < 0.05, **P < 0.01, and ***P < 0.001 versus AOPP. CON, untreated cells; MSA, mouse serum albumin.
Mentions: Next, we tested the hypothesis that SLs (MCL, compound 1, and compound 2), as derivatives of PTL, may have the same anti-inflammatory response in podocytes. After preincubation with SLs, cells were treated with 200 μg/mL AOPPs for 24 h. PTL (5 μM) was used as a positive control. The expression of MCP-1 mRNA was determined by qPCR, and MCP-1 protein expression was measured by ELISA. The results presented in Figures 4(a), 4(b), and 4(c) and Figures 5(a), 5(b), and 5(c) demonstrated that MCL, compound 1, and compound 2 responded in a dose-dependent manner to prevent the expression of MCP-1 mRNA and protein. Additionally, MCL, compound 1, and compound 2 at a concentration of 5 μM, 10 μM, and 2.5 μM, respectively, produced an almost equal inhibitory effect on MCP-1 as 5 μM of PTL.

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