Anti-TNF-α Agent Infliximab and Splenectomy Are Protective Against Renal Ischemia-Reperfusion Injury

Nagata, Yudai; Fujimoto, Mitsuaki; Nakamura, Kimihiko; Isoyama, Naohito; Matsumura, Masafumi; Fujikawa, Koki; Uchiyama, Koichi; Takaki, Eiichi; Takii, Ryosuke; Nakai, Asami; Matsuyama, Hideyasu

doi:10.1097/tp.0000000000001222

Cited by 23 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has also been demonstrated to be protective against renal ischemia-reperfusion injury. 60 In the present study, CRP (one of the indicators of an inflammatory response) was minimal under the administration of IL-6R blockade (except transiently after the operative procedures), which correlated with our previous studies. 23,53 Following xenotransplantation, we have observed a rapid decline of fT3 within hours.…”

supporting

confidence: 92%

See 1 more Smart Citation

Immunological and physiological observations in baboons with life‐supporting genetically engineered pig kidney grafts

Iwase

Hara

Ezzelarab

et al. 2017

Xenotransplantation

184

287

View full text Add to dashboard Cite

Background Genetically-engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 days and 310 days, but graft survival >30 days has been unusual until recently. Methods Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement-regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation-regulatory protein. Two baboons received a kidney from a 6-gene pig (Group A) and two from a 3-gene pig (Group B). Immunosuppressive therapy was identical in all 4 cases, and consisted of anti-thymoglobulin (ATG) + anti-CD20mAb (induction) and anti-CD40mAb + rapamycin + corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R mAbs were administered to reduce the inflammatory response. Baboons were followed by clinical/laboratory monitoring of immune/coagulation/inflammatory/physiological parameters. At biopsy or euthanasia, the grafts were examined by microscopy. Results The two Group A baboons remained healthy with normal renal function >7 and >8 months, respectively, but then developed infectious complications. However, no features of a consumptive coagulopathy, e.g., thrombocytopenia, reduction of fibrinogen, or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response, and histology of biopsies taken at approximately 4, 6, and 7 months and at necropsy showed no significant abnormalities. In contrast, both Group B baboons developed features of a consumptive coagulopathy and required euthanasia on day 12. Conclusions The combination of (i) a graft from a specific 6-gene genetically-modified pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory therapy prevented immune injury, a protein-losing nephropathy, and coagulation dysfunction for >7 months. Although the number of experiments is very limited, our impression is that expression of human endothelial protein C receptor (+/− CD55) in the graft is important if coagulation dysregulation is to be avoided.

show abstract

supporting

confidence: 92%

“…We have no personal data that tumor necrosis factor alpha (TNF‐α) is important, but its perceived benefit in islet allo‐ and xenotransplantation persuaded us to incorporate a short course in our protocol. It has also been demonstrated to be protective against renal ischemia‐reperfusion injury …”

Section: Discussionmentioning

confidence: 99%

Immunological and physiological observations in baboons with life‐supporting genetically engineered pig kidney grafts

Iwase

Hara

Ezzelarab

et al. 2017

Xenotransplantation

184

287

View full text Add to dashboard Cite

show abstract

“…Proinflammatory cytokines, such as TNF‐α and IL‐6, were upregulated in I/R‐induced acute kidney injury and produce a variety of injurious changes in proximal tubular epithelial cells . Nagata et al . reported that TNF‐α inhibition can protect the kidney from I/R injury.…”

Section: Discussionmentioning

confidence: 99%

Schisantherin A protects renal tubular epithelial cells from hypoxia/reoxygenation injury through the activation of PI3K/Akt signaling pathway

Gong

Wang

2018

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Schisantherin A (SchA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, was reported to possess anti-inflammatory and antioxidant activities. However, its protective effect against renal ischemia-reperfusion (I/R) injury in human renal tubular epithelial cells subjected to hypoxia/reoxygenation (H/R) has never been studied. Thus, herein, we investigated the effect of SchA on renal I/R injury in vitro. Our results demonstrated that SchA pretreatment significantly improved HK-2 cell viability exposed to H/R. Pretreatment with SchA markedly inhibited the levels of reactive oxygen species and malondialdehyde, as well as suppressed the production of tumor necrosis factor-α (TNF-α), interleukin-1β, and interleukin-6 in H/R-stimulated HK-2 cells. In addition, SchA also suppressed H/R-induced HK-2 cell apoptosis. Furthermore, this protective effect of SchA was mediated through the PI3K/Akt signaling pathway in HK-2 cells. These findings showed that SchA may exert a protective effect on renal tubular epithelial cells against H/R injury through the activation of PI3K/Akt signaling pathway.

show abstract

“…The down-regulation of TNF-α expression is considered beneficial to protect the kidneys from injuries. Anti-TNF-α antibodies have been reported to protect the kidney from ischemia-reperfusion injury [32]. Does TNF-α modulate MC transdifferentiation in individuals with LN through ICAM-1?…”

Section: Discussionmentioning

confidence: 99%

Emodin ameliorates renal injury in BXSB mice by modulating TNF-α/ICAM-1

et al. 2020

View full text Add to dashboard Cite

The purpose of this study was to explore the effects of emodin on renal injury in a BXSB mouse model of lupus and its mechanisms. BXSB mice were fed different concentrations of emodin (0, 5, 10 and 20 mg/kg.d), and the levels of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-alpha (TNF-α) and fibronectin (FN) levels in the glomeruli and serum levels of the anti-dsDNA antibody were determined. Mesangial cells (MCs) were cultured in vitro, and IgG-type anti-dsDNA antibody and/or emodin were added to the MC culture supernatant. In addition, a TNF-α siRNA was transfected into MCs to explore the mechanism of action of emodin. The results showed that the mice fed emodin presented decreases in the urinary protein content and glomerular TNF-α, ICAM-1 and FN levels (P<0.05). Moreover, the urine protein, TNF-α, ICAM-1 and FN levels were decreased in a dose-dependent manner (P<0.05). In vitro, the anti-dsDNA antibody group exhibited increased levels of ICAM-1 and TNF-α (P<0.05), and the anti-dsDNA antibody group showed myofibroblast-like structural changes. The aforementioned indexes were decreased in the emodin group (P<0.05), and the extent of transdifferentiation was significantly reduced. Moreover, the level of ICAM-1 decreased with the downregulation of TNF-α (P<0.05). Emodin reduced the urine protein levels and serum levels of the anti-dsDNA antibody in a mouse model of lupus nephritis (LN). The underlying mechanism may be related to decreased levels of TNF-α, ICAM-1 and FN and the inhibition of dsDNA antibody-induced MC damage.

show abstract

Anti-TNF-α Agent Infliximab and Splenectomy Are Protective Against Renal Ischemia-Reperfusion Injury

Abstract: Splenectomy and TNF-α inhibition both protect the kidney from I/R injury by reducing the accumulation of renal macrophages/monocytes and induction of major inflammatory cytokines.

Cited by 23 publications

References 31 publications

Immunological and physiological observations in baboons with life‐supporting genetically engineered pig kidney grafts

Immunological and physiological observations in baboons with life‐supporting genetically engineered pig kidney grafts

Schisantherin A protects renal tubular epithelial cells from hypoxia/reoxygenation injury through the activation of PI3K/Akt signaling pathway

Emodin ameliorates renal injury in BXSB mice by modulating TNF-α/ICAM-1

Contact Info

Product

Resources

About