Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion

Cugini, Daniela; Azzollini, Nadia; Gagliardini, Elena; Cassis, Paola; Bertini, Riccardo; Colotta, Francesco; Noris, Marina; Remuzzi, Giuseppe; Benigni, Ariela

doi:10.1111/j.1523-1755.2005.00272.x

Cited by 122 publications

(101 citation statements)

References 32 publications

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“…After IRI, an increase in the expression of IL-8/CXCL8 and Gro-␣/CXCL1 associates with marked neutrophil infiltration, 26,27 suggesting that CXCL chemokines play a significant role in neutrophil recruitment. The ability of IL-8/CXCL8 to recruit neutrophils by upregulating tubular ICAM-1, by engaging their cognate receptor, CXCR-1, to activate the p38 MAPK signaling pathway reveals an essential role of the CXCL family in the process of neutrophil recruitment.…”

Section: Role Of the Cxcl Family In Innate Immune Responses In Akimentioning

confidence: 99%

“…28 The functional role of CXCL family in AKI is clearly demonstrated by finding that treatment with a CXCR2 inhibitor or neutralizing antibodies to Gro-␣/CXCL1 or MIP-2/Gro-␤/CXCL2 during renal IRI blocks interstitial neutrophil infiltration, reduces renal damage, and improves survival. 27,26 Deficiency of IL-23, IL-17A, or IL-17 receptor, or the addition of neutralizing antibodies to CXCR2 in mice, attenuates neutrophil infiltration in IRI. 29,30 During the innate immune response in IRI, neutrophils produce a large amount of IL-17A, which in turninducesproinflammatorycytokinesand chemokine (CXCL1/2) to promote kidney inflammation.…”

Section: Role Of the Cxcl Family In Innate Immune Responses In Akimentioning

confidence: 99%

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Chemokines in Renal Injury

Chung

Lan

2011

Journal of the American Society of Nephrology

235

181

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Renal inflammation underlies many chronic kidney diseases and the infiltration of leukocytes mediates much of the nephritogenic inflammatory response. As several recent reviews have dealt with the basic biology, mouse models, and blockade studies of chemokines in renal diseases, [1][2][3][4][5][6][7][8][9][10][11] we focus here on recent developments in pathophysiology of that chemokine effect. CHEMOKINES AND CHEMOKINE RECEPTORSChemokines are a group of chemotactic cytokines (approximately 8 to 17 kD) with the ability to bind G-proteincoupled receptors and act as potent attractants for leukocytes in acute and chronic inflammation. There are four subfamilies of chemokines, including CCL, CXCL, CX3CL, and CL (Figure 1). 7,6 At present, 19 receptors are known ( Figure 1). 6,7 The large CC chemokine family has the first two cysteine residues adjacent to each other, whereas the CXC family has a single amino acid residue in between the first two cysteines. Fractalkine (CX3CL1) is the only member of the CX3C chemokine family where three amino acid residues separate the first two cysteines. Finally, two related chemokines absent the two cysteine residues that bind the XCR1 receptor belong to the XC family. As shown in Figure 1, many chemokines bind multiple receptors and most receptors bind multiple chemokines. However, CC chemokine receptors exclusively bind CC chemokines and CXC receptors bind only CXC chemokines.Chemokines and their corresponding receptors are expressed in different cell types (Figure 2). 7,12 Generally speaking, monocytes are mostly attracted by CCL chemokines acting through CCR1, CCR2, andCCR5receptors,whereasneutrophilsare the target of CXCL chemokines through REGULATION OF CHEMOKINE EXPRESSIONOn the basis of their regulation and production, chemokines can be classified broadly as homeostatic/lymphoid or inflammatory chemokines. The former is responsible for leukocyte homing and ABSTRACTThe main function of chemokines is to guide inflammatory cells in their migration to sites of inflammation. During the last 2 decades, an expanding number of chemokines and their receptors have driven broad inquiry into how inflammatory cells are recruited in a variety of diseases. Although this review focuses on chemokines and their receptors in renal injury, proinflammatory IL-17, TGF␤, and TWEAK signaling pathways also play a critical role in their expression. Recent studies in transgenic mice as well as blockade of chemokine signaling by neutralizing ligands or receptor antagonists now allow direct interrogation of chemokine action. The emerging role of regulatory T cells and Th17 cells during renal injury also forges tight relationships between chemokines and T cell infiltration in the development of kidney disease. As chemokine receptor blockade inches toward clinical use, the field remains an attractive area with potential for unexpected opportunity in the future.

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Section: Role Of the Cxcl Family In Innate Immune Responses In Akimentioning

confidence: 99%

Section: Role Of the Cxcl Family In Innate Immune Responses In Akimentioning

confidence: 99%

Chemokines in Renal Injury

Chung

Lan

2011

Journal of the American Society of Nephrology

235

181

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“…At the same time, the need to extend donor criteria in light of organ shortage further increases the risk for delayed graft function. Several approaches have already been taken to reduce early graft dysfunction, including optimization of the perfusion fluid (7,8) and the use of pharmaceuticals that interact with single steps in the pathogenesis of ischemia reperfusion injury (9). We reasoned that an effective way to improve early and possibly late graft function could be the induction of an array of endogenous protective mechanisms before the initiation of the acute injury associated with transplantation.…”

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confidence: 99%

Donor treatment with a PHD-inhibitor activating HIFs prevents graft injury and prolongs survival in an allogenic kidney transplant model

Bernhardt

Göttmann

Doyon

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

132

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“…Neutrophils could also modulate rejections of other organs and tissues transplants. In organ transplants, neutrophils could infiltrate into lungs at 6 hours in a rat lung transplantation model (8); it was verified to increased at about 2 hours after revascularization in a rat small bowel transplantation model (7); an increase of neutrophil chemoattractant CINC-1/interleukin-8 (IL-8) mRNA expression was associated with a marked infiltration of neutrophils in renal tissue at 2 hours in a rat model of ischemia/reperfusion injury followed by kidney transplant (29) and neutrophil chemoattractant growth-related oncogene alpha (KC) expression peaked at 6 h and neutrophils infiltration increased significantly 48 hours after transplant in a mice heterotopical allograft heart transplantation model (30). In other tissues transplants, neutrophils can also often be found in the early stages post-transplantation.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils infiltration is early event of an oral mucosal xenotransplantation model

Wang

Tao²,

Xiang³

et al. 2011

Med Oral

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Introduction: As important effector cells of the innate immune system, neutrophils are involved in rejection of solid organ and/or tissue transplants. But their role in rejection of oral mucosa transplantation (OMT) remains unclear. The aim of this study is to observe the spatial-temporal change of neutrophils during acute rejection of OMT. Methods: In a rat model of oral mucosal xenotransplantation, myeloperoxidase (MPO), an indicator of influx of neutrophils was detected by technique of ELISA on day 7 and 30 (D7, D30) of posttransplantation. Results: On D7, MPO level (6.183±0.416, ×10 2 ng/mg) in the OMT group was significantly higher than in trauma (0.681±0.073, ×10 2 ng/mg) and normal controls (0.262±0.043, ×10 2 ng/mg) (P<0.001, respectively), and this level was found to correlate with the index of submandibular lymph nodes (ILN), an indicator of inflammation of rejection (r=0.909, P<0.05). Moreover, this level was decreased significantly under FK506 treatment (2.103±0.146, ×10 2 ng/mg, P= 0.005). On D30, MPO in the OMT group (1.063±0.096, ×10 2 ng/mg) was lower significantly than that on D7 (P<0.001), although this level was still higher that of normal controls on D30 (0.532±0.112, ×10 2 ng/ mg, P = 0.042). Conclusion: Neutrophils infiltration was an early event of OMT, which may play important roles on acute rejection of OMT.

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Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion

Cited by 122 publications

References 32 publications

Chemokines in Renal Injury

Chemokines in Renal Injury

Donor treatment with a PHD-inhibitor activating HIFs prevents graft injury and prolongs survival in an allogenic kidney transplant model

Neutrophils infiltration is early event of an oral mucosal xenotransplantation model

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