TNF-α Neutralization Decreases Nuclear Factor-κB Activation and Apoptosis During Renal Obstruction

Meldrum, Kirstan K.; Metcalfe, Peter; Leslie, Jeffrey A.; Misseri, Rosalia; Hile, Karen L.; Meldrum, Daniel R.

doi:10.1016/j.jss.2005.11.581

Cited by 53 publications

(50 citation statements)

References 24 publications

(47 reference statements)

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“…Recent research has demonstrated that various cytokines and chemokines including TGF-b, TNF-a, and ICAM-1 are involved in renal fibrosis induced by UUO. 27,29,30 Our study also showed that ICAM-1 and TNF-a mRNA expression was upregulated in the UUO group. Furthermore, treatment with RSV markedly decreased these mRNA levels.…”

Section: Discussionsupporting

confidence: 66%

Resveratrol as a therapeutic agent for renal fibrosis induced by unilateral ureteral obstruction

et al. 2013

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Aims: Renal fibrosis is a common outcome of chronic kidney disease. This study was designed to examine the protective effects of resveratrol (RSV) against renal fibrosis induced by unilateral ureteral obstruction (UUO). We also attempted to elucidate the potential mechanism involved. Methods: Mice were randomly divided into three groups: sham-operated, UUO, and UUO/RSV (20 mgÁkg À1 Áday À1). Histological changes were examined using periodic acid-Schiff and Masson's trichrome staining after 14 days. Superoxide dismutase (SOD), malondialdehyde (MDA), and 8-OHdG levels were determined using a commercially available kit. ICAM-1, TNF-a, and TGF-b levels were measured using real-time PCR. Fibronectin levels were measured by western blot, and the Smad3 acetylation and Sirt1 were examined by immunoprecipitation and western blot. Results: Our study showed that RSV treatment significantly attenuated renal injury including extracellular matrix deposition and tubulointerstitium damage. Renal cortical mRNA levels of ICAM-1, TNF-a, and TGF-b, protein expression of fibronectin and Smad3 acetylation were significantly upregulated in the UUO group. However, treatment with RSV significantly decreased the expression of these proteins. Furthermore, RSV also decreased the levels of reactive oxygen species (ROS) including MDA and 8-OHdG, and increased the level of SOD, which protects cells against ROS damage. Conclusion: Our findings suggest that RSV treatment inhibits oxidative stress, Smad3 acetylation, and renal interstitial fibrosis. Therefore, RSV may have potential as a therapeutic target for the treatment of chronic kidney disease.

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Section: Discussionsupporting

confidence: 66%

Resveratrol as a therapeutic agent for renal fibrosis induced by unilateral ureteral obstruction

et al. 2013

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“…It has previously been shown that ANG II stimulates TNF-␣ production (18,21); however, in this investigation, we demonstrate that TNF-␣ also influences the renin-angiotensin signaling axis by increasing angiotensinogen expression. TNF-␣ induces NF-B activation during UUO (27), and it is likely through this mechanism that TNF-␣ increases angiotensinogen expression. Although the interrelationship and relative contribution of TNF-␣ and ANG II to obstruction-induced renal fibrosis warrants further investigation, it is clear, based on our observations in a physiological model of TNF-␣ inhibition, that TNF-␣ is an important mediator of obstruction-induced fibrosis.…”

Section: Discussionmentioning

confidence: 99%

TNF-α neutralization ameliorates obstruction-induced renal fibrosis and dysfunction

Meldrum¹,

Misseri²,

Metcalfe³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In contrast, initiation of C5aRA treatment before transplantation significantly reduced (P Ͻ 0.01) the frequency of TUNEL-positive cells ( Figure 4B), indicating the crucial role of C5aR in IR-induced apoptosis. Because the proinflammatory cytokine TNF-␣ is an established inducer of apoptosis 22,23 and upregulation of TNF-␣ has been demonstrated in IR injury, 24,25 we investigated the expression of TNF-␣ mRNA in allografts from vehicle-treated recipients compared with those from C5aRA-treated recipients. As expected, we observed a strong transplantinduced upregulation of TNF-␣ mRNA expression in allografts from vehicle-treated recipients at 1 d after transplantation (P Ͻ 0.01 versus control).…”

Section: C5ara Treatment Markedly Reduced Apoptosismentioning

confidence: 99%

Complement 5a Receptor Inhibition Improves Renal Allograft Survival

Gueler¹,

Rong²,

Gwinner³

et al. 2008

Journal of the American Society of Nephrology

104

116

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Complement activation plays a key role in mediating apoptosis, inflammation, and transplant rejection. In this study, the role of the complement 5a receptor (C5aR) was examined in human renal allografts and in an allogenic mouse model of renal transplant rejection. In human kidney transplants with acute rejection, C5aR expression was increased in renal tissue and in cells infiltrating the tubulointerstitium. Similar findings were observed in mice. When recipient mice were treated once daily with a C5aR antagonist before transplantation, long-term renal allograft survival was markedly improved compared with vehicle-treatment (75 versus 0%), and apoptosis was reduced. Furthermore, treatment with a C5aR antagonist significantly attenuated monocyte/macrophage infiltration, perhaps a result of reduced levels of monocyte chemoattractant protein 1 and the intercellular adhesion molecule 1. In vitro, C5aR antagonism inhibited intercellular adhesion molecule 1 upregulation in primary mouse aortic endothelial cells and reduced adhesion of peripheral blood mononuclear cells. Furthermore, C5aR blockade markedly reduced alloreactive T cell priming. These results demonstrate that C5aR plays an important role in mediating acute kidney allograft rejection, suggesting that pharmaceutical targeting of C5aR may have potential in transplantation medicine.

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TNF-α Neutralization Decreases Nuclear Factor-κB Activation and Apoptosis During Renal Obstruction

Cited by 53 publications

References 24 publications

Resveratrol as a therapeutic agent for renal fibrosis induced by unilateral ureteral obstruction

Resveratrol as a therapeutic agent for renal fibrosis induced by unilateral ureteral obstruction

TNF-α neutralization ameliorates obstruction-induced renal fibrosis and dysfunction

Complement 5a Receptor Inhibition Improves Renal Allograft Survival

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