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

AOPP-increased MCP-1 expression in podocytes was mainly mediated by the IKK/NF-κB pathway. The overnight serum-deprived podocytes were treated with 200 μg/mL AOPPs for 30 min. The expression of p-IKKα/β, p-NF-κB p65, and IκBα was examined by Western blotting (a, b, and c). To verify the role of the IKK/NF-κB pathway involved in the AOPP-induced MCP-1 expression, protein levels of MCP-1 were determined by ELISA using cell supernatants exposed to AOPPs for 24 h in the presence of the IKK/NF-κB inhibitor PTL (d). Data are expressed as the means ± SEM of three independent experiments. ANOVA, (a, b, and c) *P < 0.05, **P < 0.01 versus CON. (d) ###P < 0.001 versus CON, ***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

fig3: AOPP-increased MCP-1 expression in podocytes was mainly mediated by the IKK/NF-κB pathway. The overnight serum-deprived podocytes were treated with 200 μg/mL AOPPs for 30 min. The expression of p-IKKα/β, p-NF-κB p65, and IκBα was examined by Western blotting (a, b, and c). To verify the role of the IKK/NF-κB pathway involved in the AOPP-induced MCP-1 expression, protein levels of MCP-1 were determined by ELISA using cell supernatants exposed to AOPPs for 24 h in the presence of the IKK/NF-κB inhibitor PTL (d). Data are expressed as the means ± SEM of three independent experiments. ANOVA, (a, b, and c) *P < 0.05, **P < 0.01 versus CON. (d) ###P < 0.001 versus CON, ***P < 0.001 versus AOPP. CON, untreated cells; MSA, mouse serum albumin.

Mentions: To examine the involvement of the proinflammatory signaling pathways of IKK/NF-κB in AOPP-induced MCP-1 expression, we first examined the phosphorylation of IKKβ, degradation of IκBα, and activation of NF-κB by Western blotting. As shown above, the levels of phospho-IKKα/β and phospho-NF-κB p65 protein were upregulated by 200 μg/mL AOPPs (Figures 3(a) and 3(c)), whereas IκBα protein expression declined (Figure 3(b)) when compared to unstimulated cells or cells treated with native MSA. Total levels of IKKβ and NF-κB p65 did not significantly change among each group.


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)

AOPP-increased MCP-1 expression in podocytes was mainly mediated by the IKK/NF-κB pathway. The overnight serum-deprived podocytes were treated with 200 μg/mL AOPPs for 30 min. The expression of p-IKKα/β, p-NF-κB p65, and IκBα was examined by Western blotting (a, b, and c). To verify the role of the IKK/NF-κB pathway involved in the AOPP-induced MCP-1 expression, protein levels of MCP-1 were determined by ELISA using cell supernatants exposed to AOPPs for 24 h in the presence of the IKK/NF-κB inhibitor PTL (d). Data are expressed as the means ± SEM of three independent experiments. ANOVA, (a, b, and c) *P < 0.05, **P < 0.01 versus CON. (d) ###P < 0.001 versus CON, ***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

fig3: AOPP-increased MCP-1 expression in podocytes was mainly mediated by the IKK/NF-κB pathway. The overnight serum-deprived podocytes were treated with 200 μg/mL AOPPs for 30 min. The expression of p-IKKα/β, p-NF-κB p65, and IκBα was examined by Western blotting (a, b, and c). To verify the role of the IKK/NF-κB pathway involved in the AOPP-induced MCP-1 expression, protein levels of MCP-1 were determined by ELISA using cell supernatants exposed to AOPPs for 24 h in the presence of the IKK/NF-κB inhibitor PTL (d). Data are expressed as the means ± SEM of three independent experiments. ANOVA, (a, b, and c) *P < 0.05, **P < 0.01 versus CON. (d) ###P < 0.001 versus CON, ***P < 0.001 versus AOPP. CON, untreated cells; MSA, mouse serum albumin.
Mentions: To examine the involvement of the proinflammatory signaling pathways of IKK/NF-κB in AOPP-induced MCP-1 expression, we first examined the phosphorylation of IKKβ, degradation of IκBα, and activation of NF-κB by Western blotting. As shown above, the levels of phospho-IKKα/β and phospho-NF-κB p65 protein were upregulated by 200 μg/mL AOPPs (Figures 3(a) and 3(c)), whereas IκBα protein expression declined (Figure 3(b)) when compared to unstimulated cells or cells treated with native MSA. Total levels of IKKβ and NF-κB p65 did not significantly change among each group.

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