Endogenous Interleukin-6 Enhances the Renal Injury, Dysfunction, and Inflammation Caused by Ischemia/Reperfusion

Patel, Nimesh S. A.; Chatterjee, Prabal K.; Paola, Rosanna Di; Mazzon, Emanuela; Britti, Domenico; Sarro, Angela De; Cuzzocrea, Salvatore; Thiemermann, Christoph

doi:10.1124/jpet.104.078659

Cited by 162 publications

(137 citation statements)

References 49 publications

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“…Because inhibition of apoptosis, IL-6, or P-selectin has been demonstrated to protect against I/R-induced organ failure in the kidney, 15,[22][23][24] heart, 35,36 brain, 37,38 intestine, 39 and liver, 40 GC-G may also be involved in I/R-induced abnormalities in other organs, such as acute myocardial infarction in the heart or stroke in the brain, which warrants further investigation. Although the exact mechanism by which GC-G is regulated under renal I/R remains undefined, a simple regulatory mechanism could be that renal I/R induces the release of endogenous ligand(s) and modulates GC-G activity to transmit the injury signal leading to apoptosis and inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…34 Proinflammatory cytokine IL-6 was previously found to be produced by macrophages infiltrating adjacent to ischemic vascular bundles of the outer medulla. 22,23 A local increase in IL-6 was shown to promote PMN accumulation within the ischemic renal tissue by directly amplifying a substantial production of the proinflammatory cytokines IL-1␤ and TNF-␣ and/or an upregulation of the adhesion molecules intercellular adhesion molecule-1 and P-selectin on the endothelium. 22,23 Because we failed to localize GC-G expression in any of the infiltrating PMN or in the endothelial layer of peritubular capillaries and interlobular arteries (Figure 2, E and F), the effects of GC-G on I/R-induced inflammation might be mediated through an indirect mechanism in these cell types.…”

Section: Discussionmentioning

confidence: 99%

“…22,23 A local increase in IL-6 was shown to promote PMN accumulation within the ischemic renal tissue by directly amplifying a substantial production of the proinflammatory cytokines IL-1␤ and TNF-␣ and/or an upregulation of the adhesion molecules intercellular adhesion molecule-1 and P-selectin on the endothelium. 22,23 Because we failed to localize GC-G expression in any of the infiltrating PMN or in the endothelial layer of peritubular capillaries and interlobular arteries (Figure 2, E and F), the effects of GC-G on I/R-induced inflammation might be mediated through an indirect mechanism in these cell types. On the contrary, double immunostaining revealed that with I/R injury, GC-G and activated caspase-3 were co-localized to the same tubular cells (data not shown), which suggests that GC-Gmediated programmed cell death occurs primarily in renal tubular epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…19 -24 For example, expression of adhesion molecule P-selectin and proinflammatory cytokine IL-6 is induced in ischemic renal tissues, and its inhibition protects against I/R-induced renal failure in mice. [22][23][24] We thus compared the expression of P-selectin and IL-6 in kidneys of WT and GC-G Ϫ/Ϫ mice subjected to renal I/R. GC-G Ϫ/Ϫ mice showed marked reduction in P-selectin and IL-6 mRNA level as compared with WT controls ( Figure 6A).…”

Section: Decreased Number Of Polymorphonuclear Cells and Renal Myelopmentioning

confidence: 99%

“…Male mice, ages approximately 8 to 10 wk, were subjected to bilateral renal artery occlusion (45 min) and reperfusion (24 h) as described previously. 23 Sham control animals underwent the identical surgery except for pedicle clamping.…”

Section: Animal Model For Renal I/rmentioning

confidence: 99%

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Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Lin

Cheng²,

Hou

et al. 2008

Journal of the American Society of Nephrology

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The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G Ϫ/Ϫ mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G Ϫ/Ϫ mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-B were lower in GC-G Ϫ/Ϫ mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G Ϫ/Ϫ mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Decreased Number Of Polymorphonuclear Cells and Renal Myelopmentioning

confidence: 99%

Section: Animal Model For Renal I/rmentioning

confidence: 99%

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Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Lin

Cheng²,

Hou

et al. 2008

Journal of the American Society of Nephrology

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Immune and Inflammatory Role in Renal Disease

Imig

Ryan

2013

Comprehensive Physiology

293

210

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Chronic and acute renal diseases, irrespective of the initiating cause, have inflammation and immune system activation as a common underlying mechanism. The purpose of this review is to provide a broad overview of immune cells and inflammatory proteins that contribute to the pathogenesis of renal disease, and to discuss some of the physiological changes that occur in the kidney as a result of immune system activation. An overview of common forms of acute and chronic renal disease is provided, followed by a discussion of common therapies that have antiinflammatory or immunosuppressive effects in the treatment of renal disease.

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Evodiamine alleviates kidney ischemia reperfusion injury in rats: A biochemical and histopathological study

Eraslan

Tanyeli

Polat

et al. 2019

J of Cellular Biochemistry

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Renal ischemia/reperfusion (I/R) injury resulting in acute renal failure, is a major clinical problem due to its high mortality rate. Renal I/R increases the reactive oxygen species, secretion of inflammatory cytokines, chemokines and other factors. This suggests that initiating the apoptosis process in the presence of oxidative stress may play a role in life‐threatening conditions, such as ischemia. Ischemia reperfusion‐induced renal damage can result in renal failure and death. Although many treatment procedures have been carried out to reduce or destroy renal I/R damage in experimental models, so far, a routine method of treatment has not yet been found. For this reason, the current study was planned to investigate the possible protective effects of evodiamine on tissue damage caused by ischemia‐reperfusion in kidney tissue in rats and an experimental renal I/R model was used for this purpose. Four groups were formed in the study: the control, sham control, ischemia reperfusion (I/R), and evodiamine (10 mg/kg) + I/R groups. The effects of evodiamine against kidney I/R injury were investigated. TAS (total oxidant status), TOS (total oxidant status), interleukin‐1β (IL‐1β), IL‐6, IL‐10 and tumor necrosis factor‐α levels were determined by enzyme‐linked immunosorbent assay. The oxidative stress index was calculated from TAS and TOS levels. In addition, the renal ischemia reperfusion injury was examined histopathologically. The IL‐10 and TAS levels in the I/R group decreased when compared with the control and Sham groups, while these levels increased in the evodiamine group. Histopathologic examination revealed that caspase 3 and nuclear factor‐κB levels decreased in the evodiamine group compared with the I/R group. The application of evodiamine significantly reduced ischemia reperfusion‐induced kidney damage due to its antioxidant, anti‐inflammatory and antiapoptotic properties.

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Endogenous Interleukin-6 Enhances the Renal Injury, Dysfunction, and Inflammation Caused by Ischemia/Reperfusion

Cited by 162 publications

References 49 publications

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Immune and Inflammatory Role in Renal Disease

Evodiamine alleviates kidney ischemia reperfusion injury in rats: A biochemical and histopathological study

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