Limits...
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 treatment suppressed the activation of the NF-κB and JNK/p38 MAPK signaling pathways. Crude proteins obtained from the kidney tissues of vehicle- and DHMEQ-treated mice were analyzed by western blot analysis using specific antibodies against (A) NF-κB p65 and (B) p-JNK and p-p38 MAPK. Quantitative analysis was performed by densitometry using an internal control. *P<0.01, vs. vehicle-treated control. DHMEQ, dehydroxymethylepoxyquinomicin; NF, nuclear factor; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; p-JNK, phosphorylated-JNK; p-p38, phosphorylated-p38.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4061236&req=5

f4-etm-08-01-0100: DHMEQ treatment suppressed the activation of the NF-κB and JNK/p38 MAPK signaling pathways. Crude proteins obtained from the kidney tissues of vehicle- and DHMEQ-treated mice were analyzed by western blot analysis using specific antibodies against (A) NF-κB p65 and (B) p-JNK and p-p38 MAPK. Quantitative analysis was performed by densitometry using an internal control. *P<0.01, vs. vehicle-treated control. DHMEQ, dehydroxymethylepoxyquinomicin; NF, nuclear factor; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; p-JNK, phosphorylated-JNK; p-p38, phosphorylated-p38.

Mentions: To further explore the underlying mechanism, the expression levels of associated signaling molecules in the renal tissue were analyzed. A previous study indicated that the inflammation-mediated activation of the JNK and p38 MAPK signaling pathways may be the underlying intracellular mechanism causing lymphocyte hyperactivity in SLE (12). NF-κB p65, an indicator of NF-κB signaling activation, was found to be downregulated by DHMEQ treatment (Fig. 4A). In addition, the phosphorylation levels of JNK and p38 MAPK in the renal tissues of the mice with pristane-induced lupus were significantly decreased following DHMEQ treatment (Fig. 4B). These results indicate that the treatment effects of DHMEQ are associated with JNK/p38 MAPK signaling in mouse SLE.


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

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

DHMEQ treatment suppressed the activation of the NF-κB and JNK/p38 MAPK signaling pathways. Crude proteins obtained from the kidney tissues of vehicle- and DHMEQ-treated mice were analyzed by western blot analysis using specific antibodies against (A) NF-κB p65 and (B) p-JNK and p-p38 MAPK. Quantitative analysis was performed by densitometry using an internal control. *P<0.01, vs. vehicle-treated control. DHMEQ, dehydroxymethylepoxyquinomicin; NF, nuclear factor; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; p-JNK, phosphorylated-JNK; p-p38, phosphorylated-p38.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-etm-08-01-0100: DHMEQ treatment suppressed the activation of the NF-κB and JNK/p38 MAPK signaling pathways. Crude proteins obtained from the kidney tissues of vehicle- and DHMEQ-treated mice were analyzed by western blot analysis using specific antibodies against (A) NF-κB p65 and (B) p-JNK and p-p38 MAPK. Quantitative analysis was performed by densitometry using an internal control. *P<0.01, vs. vehicle-treated control. DHMEQ, dehydroxymethylepoxyquinomicin; NF, nuclear factor; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; p-JNK, phosphorylated-JNK; p-p38, phosphorylated-p38.
Mentions: To further explore the underlying mechanism, the expression levels of associated signaling molecules in the renal tissue were analyzed. A previous study indicated that the inflammation-mediated activation of the JNK and p38 MAPK signaling pathways may be the underlying intracellular mechanism causing lymphocyte hyperactivity in SLE (12). NF-κB p65, an indicator of NF-κB signaling activation, was found to be downregulated by DHMEQ treatment (Fig. 4A). In addition, the phosphorylation levels of JNK and p38 MAPK in the renal tissues of the mice with pristane-induced lupus were significantly decreased following DHMEQ treatment (Fig. 4B). These results indicate that the treatment effects of DHMEQ are associated with JNK/p38 MAPK signaling in mouse SLE.

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