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Methylprednisolone attenuates lipopolysaccharide-induced Fractalkine expression in kidney of Lupus-prone MRL/lpr mice through the NF-kappaB pathway.

You Y, Qin Y, Lin X, Yang F, Li J, Sooranna SR, Pinhu L - BMC Nephrol (2015)

Bottom Line: One-way ANOVA was used for data analysis and P value <0.05 was considered statistically significantly.The expression of FKN protein and the activation of NF-kappaB p65 were detected by immunohistochemistry and western blots respectively.MP as well as the NF-kappaB inhibitor, SC-514, inhibited the LPS-induced increase of expression of FKN and the activation of NF-kappaB.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi Zhuang Autonomous Region, China. 13977621808@163.com.

ABSTRACT

Background: Fractalkine (FKN) is involved in the occurrence and development of human lupus nephritis. It is known to be upregulated by lipopolysaccharide (LPS) as a stimulus in vivo. MRL/lpr mice have been used as an in vivo model to study lupus nephritis. Methylprednisolone (MP) is used widely in the clinical treatment of progressive glomerular diseases such as lupus nephritis. The aim of this study is to explore the mechanism of LPS induced FKN expression and to determine whether other molecular mechanisms contribute to the signaling pathway of MP action in MRL/lpr mice.

Methods: Forty-eight female MRL/lpr mice at 12 weeks of age were randomly distributed into six groups. Each group received various treatments for 8 weeks by receiving twice weekly intraperitoneal injections of (1) MP (MP-treated mice), of (2) SC-514 (SC-514-induced mice), of (3) normal saline and a single injection of LPS (LPS-induced mice), of (4) MP and a single injection of LPS (LPS + MP mice), of (5) SC-514 and a single injection of LPS (LPS + SC mice) and of (6) normal saline (control mice). One-way ANOVA was used for data analysis and P value <0.05 was considered statistically significantly.

Results: The expression of FKN and NF-kappaB p65 mRNA was detected by qPCR. The expression of FKN protein and the activation of NF-kappaB p65 were detected by immunohistochemistry and western blots respectively. The expression of FKN in the kidney of LPS induced mice was significantly increased and this was mediated by increased expression of NF-κB p65 and an increase in NF-kappaB phospho-p65. MP reduced proteinuria and ameliorated the renal damage in MRL/lpr mice. MP as well as the NF-kappaB inhibitor, SC-514, inhibited the LPS-induced increase of expression of FKN and the activation of NF-kappaB.

Conclusions: The results indicate that MP attenuates LPS-induced FKN expression in kidney of MRL/lpr mice through the NF-kappaB pathway.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemistry for p65 within glomerular lesions in MRL/lpr mice. a Control mice, b LPS-induced mice, c MP-treated mice, d SC-514-treated mice, e LPS + MP-treated mice, f LPS + SC-treated mice (original magnification, ×400)
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Fig5: Immunohistochemistry for p65 within glomerular lesions in MRL/lpr mice. a Control mice, b LPS-induced mice, c MP-treated mice, d SC-514-treated mice, e LPS + MP-treated mice, f LPS + SC-treated mice (original magnification, ×400)

Mentions: In kidney sections of MRL/lpr mice stained by IHC, the expression of FKN and p65 protein was seen mainly in the cytoplasm of podocytes, endothelial cells in glomerular and some renal tubular epithelial cells (Figs. 4 and 5). The expression of FKN and p65 protein was compared between the different groups of mice. According to semiquantitative evaluation, the intensity scores of FKN were 142.5 ± 38.7, 196.7 ± 36.5, 96.3 ± 21.6, 99.3 ± 21.5, 102.8 ± 32.4 and 118.7 ± 29.5 in control, LPS-induced, MP-treated SC-514-treated, LPS + MP and LPS + SC mice respectively. The intensity scores of p65 were 98.2 ± 32.5, 143.8 ± 44.2, 62.3 ± 18.5, 58.5 ± 17.7, 75.2 ± 21.3 and 74.5 ± 22.6 in control, LPS-induced, MP-treated SC-514-treated, LPS + MP and LPS + SC mice respectively. There was increased expression of glomerular FKN and p65 protein in LPS-induced mice (P < 0.01 and P < 0.05 respectively) when compared to control mice, a decreased expression in MP-treated mice compared to control mice (P < 0.05) and a decreased expression in LPS + MP and LPS + SC mice compared to LPS-induced mice (P < 0.01 and P < 0.05 respectively).Fig. 4


Methylprednisolone attenuates lipopolysaccharide-induced Fractalkine expression in kidney of Lupus-prone MRL/lpr mice through the NF-kappaB pathway.

You Y, Qin Y, Lin X, Yang F, Li J, Sooranna SR, Pinhu L - BMC Nephrol (2015)

Immunohistochemistry for p65 within glomerular lesions in MRL/lpr mice. a Control mice, b LPS-induced mice, c MP-treated mice, d SC-514-treated mice, e LPS + MP-treated mice, f LPS + SC-treated mice (original magnification, ×400)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4551515&req=5

Fig5: Immunohistochemistry for p65 within glomerular lesions in MRL/lpr mice. a Control mice, b LPS-induced mice, c MP-treated mice, d SC-514-treated mice, e LPS + MP-treated mice, f LPS + SC-treated mice (original magnification, ×400)
Mentions: In kidney sections of MRL/lpr mice stained by IHC, the expression of FKN and p65 protein was seen mainly in the cytoplasm of podocytes, endothelial cells in glomerular and some renal tubular epithelial cells (Figs. 4 and 5). The expression of FKN and p65 protein was compared between the different groups of mice. According to semiquantitative evaluation, the intensity scores of FKN were 142.5 ± 38.7, 196.7 ± 36.5, 96.3 ± 21.6, 99.3 ± 21.5, 102.8 ± 32.4 and 118.7 ± 29.5 in control, LPS-induced, MP-treated SC-514-treated, LPS + MP and LPS + SC mice respectively. The intensity scores of p65 were 98.2 ± 32.5, 143.8 ± 44.2, 62.3 ± 18.5, 58.5 ± 17.7, 75.2 ± 21.3 and 74.5 ± 22.6 in control, LPS-induced, MP-treated SC-514-treated, LPS + MP and LPS + SC mice respectively. There was increased expression of glomerular FKN and p65 protein in LPS-induced mice (P < 0.01 and P < 0.05 respectively) when compared to control mice, a decreased expression in MP-treated mice compared to control mice (P < 0.05) and a decreased expression in LPS + MP and LPS + SC mice compared to LPS-induced mice (P < 0.01 and P < 0.05 respectively).Fig. 4

Bottom Line: One-way ANOVA was used for data analysis and P value <0.05 was considered statistically significantly.The expression of FKN protein and the activation of NF-kappaB p65 were detected by immunohistochemistry and western blots respectively.MP as well as the NF-kappaB inhibitor, SC-514, inhibited the LPS-induced increase of expression of FKN and the activation of NF-kappaB.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi Zhuang Autonomous Region, China. 13977621808@163.com.

ABSTRACT

Background: Fractalkine (FKN) is involved in the occurrence and development of human lupus nephritis. It is known to be upregulated by lipopolysaccharide (LPS) as a stimulus in vivo. MRL/lpr mice have been used as an in vivo model to study lupus nephritis. Methylprednisolone (MP) is used widely in the clinical treatment of progressive glomerular diseases such as lupus nephritis. The aim of this study is to explore the mechanism of LPS induced FKN expression and to determine whether other molecular mechanisms contribute to the signaling pathway of MP action in MRL/lpr mice.

Methods: Forty-eight female MRL/lpr mice at 12 weeks of age were randomly distributed into six groups. Each group received various treatments for 8 weeks by receiving twice weekly intraperitoneal injections of (1) MP (MP-treated mice), of (2) SC-514 (SC-514-induced mice), of (3) normal saline and a single injection of LPS (LPS-induced mice), of (4) MP and a single injection of LPS (LPS + MP mice), of (5) SC-514 and a single injection of LPS (LPS + SC mice) and of (6) normal saline (control mice). One-way ANOVA was used for data analysis and P value <0.05 was considered statistically significantly.

Results: The expression of FKN and NF-kappaB p65 mRNA was detected by qPCR. The expression of FKN protein and the activation of NF-kappaB p65 were detected by immunohistochemistry and western blots respectively. The expression of FKN in the kidney of LPS induced mice was significantly increased and this was mediated by increased expression of NF-κB p65 and an increase in NF-kappaB phospho-p65. MP reduced proteinuria and ameliorated the renal damage in MRL/lpr mice. MP as well as the NF-kappaB inhibitor, SC-514, inhibited the LPS-induced increase of expression of FKN and the activation of NF-kappaB.

Conclusions: The results indicate that MP attenuates LPS-induced FKN expression in kidney of MRL/lpr mice through the NF-kappaB pathway.

No MeSH data available.


Related in: MedlinePlus