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A novel NF-κB inhibitor, DHMEQ, ameliorates pristane-induced lupus in mice.

Qu H, Bian W, Xu Y - Exp Ther Med (2014)

Bottom Line: In addition, DHMEQ reduced the number of renal lesions caused by pristane, as reflected by milder proteinuria and reduced renal pathology.The renal expression levels of phosphorylated-p38 mitogen-activated protein kinase (MAPK), phosphorylated-c-Jun N-terminal kinase (JNK) and NF-κB p65 were significantly downregulated.Therefore, the results of the present study indicate that DHMEQ has a beneficial effect on pristane-induced lupus through regulating cytokine levels and the MAPK/JNK/NF-κB signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Blood Transfusion, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, P.R. China.

ABSTRACT
Nuclear factor (NF)-κB is strongly associated with the development of immune regulation and inflammation. The aim of the present study was to identify whether a NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), ameliorates systemic lupus erythematosus (SLE) in a pristane-induced mouse model. SLE was induced in 8-week-old female BALB/c mice by the injection of 0.5 ml pristane. The therapeutic effect of 12 mg/kg DHMEQ on the pristane-induced BALB/c mouse model of lupus was investigated to elucidate the effects on SLE. The intraperitoneal administration of DHMEQ three times per week was initiated when the mice were 16 weeks-old (8 weeks following the pristane injection) and the treatment was continued for 16 weeks. Serum IgG autoantibodies against nucleosomes, dsDNA and histones were detected at weeks 8, 16 and 32. In addition, the expression levels of interleukin (IL)-1β, 6 and 17, as well as tumor necrosis factor (TNF)-α, were analyzed at week 32. Renal lesions were also observed. DHMEQ was shown to antagonize the increasing levels of anti-nucleosome, anti-dsDNA and anti-histone autoantibodies, as well as the increasing levels of IL-1β, 6 and 17 and TNF-α. In addition, DHMEQ reduced the number of renal lesions caused by pristane, as reflected by milder proteinuria and reduced renal pathology. The renal expression levels of phosphorylated-p38 mitogen-activated protein kinase (MAPK), phosphorylated-c-Jun N-terminal kinase (JNK) and NF-κB p65 were significantly downregulated. Therefore, the results of the present study indicate that DHMEQ has a beneficial effect on pristane-induced lupus through regulating cytokine levels and the MAPK/JNK/NF-κB signaling pathway.

No MeSH data available.


Related in: MedlinePlus

DHMEQ reduced the serum levels of (A) anti-dsDNA, (B) anti-nucleosome and (C) anti-histone autoantibodies in mice with pristane-induced lupus. Serum samples from the mice in each group were collected at weeks 8 (baseline), 16 (prior to treatment) and 32 and the antibody levels were detected by enzyme-linked immunosorbent assays. Optical density (OD) was calculated at 490 nm. Data are presented as mean ± SEM (n=12 per group). #P<0.01, vs. baseline at week 8; *P<0.01, vs. vehicle-treated model control mice. DHMEQ, dehydroxymethylepoxyquinomicin.
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f1-etm-08-01-0100: DHMEQ reduced the serum levels of (A) anti-dsDNA, (B) anti-nucleosome and (C) anti-histone autoantibodies in mice with pristane-induced lupus. Serum samples from the mice in each group were collected at weeks 8 (baseline), 16 (prior to treatment) and 32 and the antibody levels were detected by enzyme-linked immunosorbent assays. Optical density (OD) was calculated at 490 nm. Data are presented as mean ± SEM (n=12 per group). #P<0.01, vs. baseline at week 8; *P<0.01, vs. vehicle-treated model control mice. DHMEQ, dehydroxymethylepoxyquinomicin.

Mentions: The production of numerous autoantibodies is a key feature of SLE and is associated with renal damage. Serum IgG autoantibodies against nucleosomes, dsDNA and histones were detected at weeks 8, 16 and 32. There were marked increases in the serum anti-dsDNA antibody levels of the vehicle-treated model group at weeks 16 and 32, whereas the DHMEQ-treated group had markedly reduced anti-dsDNA antibody levels compared with those in the vehicle-treated model group at week 32 (Fig. 1A). Similarly, serum anti-nucleosome and anti-histone antibody levels were also significantly reduced by DHMEQ treatment when compared with those in the vehicle-treated control group at week 32 (Fig. 1B and C).


A novel NF-κB inhibitor, DHMEQ, ameliorates pristane-induced lupus in mice.

Qu H, Bian W, Xu Y - Exp Ther Med (2014)

DHMEQ reduced the serum levels of (A) anti-dsDNA, (B) anti-nucleosome and (C) anti-histone autoantibodies in mice with pristane-induced lupus. Serum samples from the mice in each group were collected at weeks 8 (baseline), 16 (prior to treatment) and 32 and the antibody levels were detected by enzyme-linked immunosorbent assays. Optical density (OD) was calculated at 490 nm. Data are presented as mean ± SEM (n=12 per group). #P<0.01, vs. baseline at week 8; *P<0.01, vs. vehicle-treated model control mice. DHMEQ, dehydroxymethylepoxyquinomicin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061236&req=5

f1-etm-08-01-0100: DHMEQ reduced the serum levels of (A) anti-dsDNA, (B) anti-nucleosome and (C) anti-histone autoantibodies in mice with pristane-induced lupus. Serum samples from the mice in each group were collected at weeks 8 (baseline), 16 (prior to treatment) and 32 and the antibody levels were detected by enzyme-linked immunosorbent assays. Optical density (OD) was calculated at 490 nm. Data are presented as mean ± SEM (n=12 per group). #P<0.01, vs. baseline at week 8; *P<0.01, vs. vehicle-treated model control mice. DHMEQ, dehydroxymethylepoxyquinomicin.
Mentions: The production of numerous autoantibodies is a key feature of SLE and is associated with renal damage. Serum IgG autoantibodies against nucleosomes, dsDNA and histones were detected at weeks 8, 16 and 32. There were marked increases in the serum anti-dsDNA antibody levels of the vehicle-treated model group at weeks 16 and 32, whereas the DHMEQ-treated group had markedly reduced anti-dsDNA antibody levels compared with those in the vehicle-treated model group at week 32 (Fig. 1A). Similarly, serum anti-nucleosome and anti-histone antibody levels were also significantly reduced by DHMEQ treatment when compared with those in the vehicle-treated control group at week 32 (Fig. 1B and C).

Bottom Line: In addition, DHMEQ reduced the number of renal lesions caused by pristane, as reflected by milder proteinuria and reduced renal pathology.The renal expression levels of phosphorylated-p38 mitogen-activated protein kinase (MAPK), phosphorylated-c-Jun N-terminal kinase (JNK) and NF-κB p65 were significantly downregulated.Therefore, the results of the present study indicate that DHMEQ has a beneficial effect on pristane-induced lupus through regulating cytokine levels and the MAPK/JNK/NF-κB signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Blood Transfusion, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, P.R. China.

ABSTRACT
Nuclear factor (NF)-κB is strongly associated with the development of immune regulation and inflammation. The aim of the present study was to identify whether a NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), ameliorates systemic lupus erythematosus (SLE) in a pristane-induced mouse model. SLE was induced in 8-week-old female BALB/c mice by the injection of 0.5 ml pristane. The therapeutic effect of 12 mg/kg DHMEQ on the pristane-induced BALB/c mouse model of lupus was investigated to elucidate the effects on SLE. The intraperitoneal administration of DHMEQ three times per week was initiated when the mice were 16 weeks-old (8 weeks following the pristane injection) and the treatment was continued for 16 weeks. Serum IgG autoantibodies against nucleosomes, dsDNA and histones were detected at weeks 8, 16 and 32. In addition, the expression levels of interleukin (IL)-1β, 6 and 17, as well as tumor necrosis factor (TNF)-α, were analyzed at week 32. Renal lesions were also observed. DHMEQ was shown to antagonize the increasing levels of anti-nucleosome, anti-dsDNA and anti-histone autoantibodies, as well as the increasing levels of IL-1β, 6 and 17 and TNF-α. In addition, DHMEQ reduced the number of renal lesions caused by pristane, as reflected by milder proteinuria and reduced renal pathology. The renal expression levels of phosphorylated-p38 mitogen-activated protein kinase (MAPK), phosphorylated-c-Jun N-terminal kinase (JNK) and NF-κB p65 were significantly downregulated. Therefore, the results of the present study indicate that DHMEQ has a beneficial effect on pristane-induced lupus through regulating cytokine levels and the MAPK/JNK/NF-κB signaling pathway.

No MeSH data available.


Related in: MedlinePlus