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Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis.

ABSTRACT: Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular- superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the synovial tissue of experimental arthritis was investigated using EC-SOD over-expressing transgenic mice. The over-expression of EC- SOD in joint tissue was confirmed by RT-PCR and immunohistochemistry. The degree of the inflammation in EC-SOD transgenic mice was suppressed in the collagen-induced arthritis model. In a cytokine assay, the production of pro-inflammatory cytokines such as, IL-1?, TNF?, and matrix metalloproteinases (MMPs) was decreased in fibroblast-like synoviocyte (FLS) but not in peripheral blood. Histological examination also showed repressed cartilage destruction and bone in EC-SOD transgenic mice. In conclusion, these data suggest that the over-expression of EC-SOD in FLS contributes to the activation of FLS and protection from joint destruction by depressing the production of the pro-inflammatory cytokines and MMPs. These results provide EC-SOD transgenic mice with a useful animal model for inflammatory arthritis research.

SUBMITTER: Yu DH

PROVIDER: S-EPMC3465746 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis.

Yu Dong Hoon DH Yi Jun Koo JK Yuh Hyung Soo HS Park Seo jin Sj Kim Hei Jung HJ Bae Ki Beom KB Ji Young Rae YR Kim Na Ri NR Park Si Jun SJ Kim Do Hyung DH Kim Sung Hyun SH Kim Myoung Ok MO Lee Jeong Woong JW Ryoo Zae Young ZY

Experimental & molecular medicine 20120901 9

Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular- superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the sy ...[more]

PMID: 22718219

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Project description:AIMS:Oxidative stress plays a crucial role in the pathogenesis of diabetic nephropathy (DN). We evaluated whether extracellular superoxide dismutase (EC-SOD) has a renoprotective effect through activation of adenosine monophosphate-activated protein kinase (AMPK) in diabetic kidneys. RESULTS:Human recombinant EC-SOD (hEC-SOD) was administered to 8-week-old male C57BLKS/J db/db mice through intraperitoneal injection once a week for 8 weeks. Renal SOD3 expression was suppressed in db/db mice, which was significantly enhanced by hEC-SOD treatment. hEC-SOD improved albuminuria, mesangial expansion, and interstitial fibrosis in db/db mice. At the molecular level, hEC-SOD increased phosphorylation of AMPK, activation of peroxisome proliferative-activated receptor ? coactivator 1? (PGC-1?), and dephosphorylation of forkhead box O transcription factor (FoxO)1 and FoxO3a. The protective effects of hEC-SOD were attributed to enhanced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased expression of NAD(P)H dehydrogenase 1 and heme oxygenase-1. Consequently, hEC-SOD recovered from systemic and renal inflammation and apoptosis, as reflected by the decreases of serum and renal monocyte chemoattractant protein-1 and tumor necrosis factor-? levels and increases of BCL-2/BAX ratio in diabetic kidney. hEC-SOD also improved oxidative stress and resulted in increased renal and urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane levels in db/db mice. In cultured human glomerular endothelial cells, hEC-SOD ameliorated apoptosis and oxidative stress caused by high glucose exposure through activation of AMPK and PGC-1? and dephosphorylation of FoxOs. INNOVATION:These findings demonstrated for the first time that EC-SOD can potentially ameliorate hyperglycemia-induced oxidative stress, apoptosis, and inflammation through activation of AMPK and its downstream pathways in diabetic kidneys. CONCLUSIONS:EC-SOD is a potential therapeutic target for treatment of type 2 DN through intrarenal AMPK-PGC-1?-Nrf2 and AMPK-FoxOs signaling. Antioxid. Redox Signal. 28, 1543-1561.

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Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis.

Publications

Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis.

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