A sphingosine-1-phosphate type 1 receptor agonist inhibits the early T-cell transient following renal ischemia–reperfusion injury

Lai, Li‐Wen; Yong, Kim Chong; Igarashi, Suzu; Lien, Yeong‐Hau H.

doi:10.1038/sj.ki.5002203

Cited by 68 publications

(78 citation statements)

References 44 publications

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“…Analysis of kidneys by light microscopy revealed minimal histologic signs of ischemic injury with FTY720 or SEW2871 treatment compared to vehicle group. Using RT-PCR, we found a time-dependent increase in the S1P 1 mRNA expression following IRI that begins after 2 h with the maximum expression at ∼4 h. Additional studies have confirmed these initial findings [64,65]. Although we believe that FTY720 through S1P 1 receptors induces inhibition of initiation of early events of T cell function, it may also induce direct protective effects on tubules.…”

Section: S1p1 Receptors In Akisupporting

confidence: 71%

Targeting sphingosine 1 phosphate receptor type 1 receptors in acute kidney injury

Okusa

Lynch

2007

Drug Discovery Today: Disease Mechanisms

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Sphingosine 1-phosphate analogs have a multitude of effects with the best characterized one being mediated through sphingosine 1-phosphate type 1 receptors (S1P1 receptor). Currently, S1P1 receptor agonists are being developed and tested for human disease. Because of the potent effect of S1P1 agonists to modulate the immune system, these compounds are ideal for blocking immune mechanisms that mediate acute kidney injury (AKI). This disorder continues to remain an important disease that is characterized by high morbidity and mortality. Currently there are no FDA approved drugs for the treatment of AKI. This review summarizes current knowledge on the mechanism of AKI due to ischemia-reperfusion and early studies that target S1P1 receptors for the treatment and prevention of AKI.Acute kidney injury (AKI) is a burgeoning medical disease. Based upon the National Health Statistics and National Hospital Discharge Survey, between 1979 and 2002 there has been an increase in hospitalization for AKI (ICD9 = 584.0 through 584.9) from 35,000 to 650,000 cases per year (P. Eggers, Am Soc. Nephrol., 2004). Overall mortality has been reported to be 40-60% in critically ill patients [1][2][3]. The estimated annual health care expenditures attributed to hospital-acquired AKI exceed $10 billion [4]. Furthermore there is recognition that there is an increase in the end stage renal disease (ESRD) population due to AKI. In patients suffering from AKI, 13.4% of patients (or 30% of patients with AKI superimposed on chronic kidney disease) will progress to ESRD in 3 years (P. Eggers, Am Soc. Nephrol, 2004). Thus to overcome barriers to successful treatment of AKI, well designed clinical trials will need to be based on a precise understanding of the molecular, cellular and immunological basis of AKI [5]. Novel pharmacological agents need to be tested in preclinical and clinical trials. This review focuses on the pathogenesis of ischemia-reperfusion and one class of agents, agonists of sphingosine 1-phosphate receptors, that are potential agents in the treatment of AKI. Pathogenesis of acute kidney ischemia reperfusion injuryAKI from ischemia is initiated by unfavorable changes in renal blood flow as a consequence of vasospasm, alterations in ultrafiltration coefficient, tubular obstruction and/or back-leak. The renal medulla is particularly susceptible to renal ischemia because of a low oxygen tension (PO 2 of 10-20 mmHg) [6]. With loss of blood flow, oxygen content is reduced even farther due to red blood cell and leukocyte trapping and a decrease in medullary blood flow. Hypoxic injury or reperfusion injury results in endothelial cell dysfunction that alters the balance of vascular tone of vasoactive agents such as endothelin and nitric oxide [7,8,[9][10][11]. In addition Dendritic cell activation of NKT cells and IFN-γ in kidney IRITissue resident macrophages and dendritic cells originate from a heterogeneous population of bone marrow-derived monocytes [23][24][25][26] Sphingosine 1-phosphate (S1P) receptors and analogsSphing...

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Section: S1p1 Receptors In Akisupporting

confidence: 71%

Targeting sphingosine 1 phosphate receptor type 1 receptors in acute kidney injury

Okusa

Lynch

2007

Drug Discovery Today: Disease Mechanisms

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“…Hence, chemokines should have a significant effect on the migration of macrophages, neutrophils, NK cells, and T cells during kidney IRI. However, as demonstrated in our study and others, leukocytes infiltrate into the kidney as quickly as 30 min to 4 h (14,14,18,24) suggesting that factors that promote injury must be rapidly upregulated or released within the kidney. Naive kidneys express OPN as confirmed in the current study ( Fig.…”

Section: Discussionmentioning

confidence: 88%

“…As shown in Fig. 2A (11)(12)(13)(14)(15)(16)(17)(18). However, infiltrating leukocytes appear to return to previous basal levels by 24 h after injury.…”

Section: Opn Deficiency Leads To Less Kidney Injurymentioning

confidence: 94%

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Osteopontin Expressed in Tubular Epithelial Cells Regulates NK Cell-Mediated Kidney Ischemia Reperfusion Injury

Zhang

Shek

Wang

et al. 2010

The Journal of Immunology

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Renal ischemia reperfusion injury (IRI) occurs after reduced renal blood flow and is a major cause of acute injury in both native and transplanted kidneys. Studies have shown diverse cell types in both the innate and the adaptive immune systems participate in kidney IRI as dendritic cells, macrophages, neutrophils, B cells, CD4+ NK+ cells, and CD4+ T cells all contribute to this form of injury. Recently, we have found that NK cells induce apoptosis in tubular epithelial cells (TECs) and also contribute to renal IRI. However, the mechanism of NK cell migration and activation during kidney IRI remains unknown. In this study, we have identified that kidney TECs express a high level of osteopontin (OPN) in vitro and in vivo. C57BL/6 OPN-deficient mice have reduced NK cell infiltration with less tissue damage compared with wild-type C57BL/6 mice after ischemia. OPN can directly activate NK cells to mediate TEC apoptotic death and can also regulate chemotaxis of NK cells to TECs. Taken together, our study’s results indicate that OPN expression by TECs is an important factor in initial inflammatory responses that involves NK cells activity in kidney IRI. Inhibiting OPN expression at an early stage of IRI may be protective and preserve kidney function after transplantation.

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“…8,9) Therefore, it is not surprising that S1P affects the immune system and has been implicated in inflammatory diseases, such as multiple sclerosis, renal ischemia-reperfusion injury, and influenza virus infection. [10][11][12][13][14] Recently, it has been reported that FTY720, a non-selective S1P receptor agonist, can attenuate pancreatic inflammation and fibrosis in the chronic pancreatitis in rats, 15) ameliorate the severity of taurocholate-induced severe acute pancreatitis (SAP), 16) and decrease pulmonary inflammation and injury in a rat model of acute lung injury caused by acute necrotizing pancreatitis. 17) However, non-selective S1P receptor agonists showed an obvious disadvantage of leading to sinus bradycardia as a complication of the activation of type-3 S1P receptors (S1P3), which may result in poor usability in the early phase of AP.…”

mentioning

confidence: 99%

SEW2871 Alleviates the Severity of Caerulein-Induced Acute Pancreatitis in Mice

Zou

et al. 2015

Biological & Pharmaceutical Bulletin

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Sphingosine-1-phosphate type-1 receptor (S1P1) agonists have the potential to inhibit the egress of lymphocytes, and have been demonstrated to provide protective effects on some acute inflammatory diseases. However, the value of S1P1 agonists on acute pancreatitis (AP) remains unclear. The aim of this study was to explore the effect of SEW2871, a S1P1-selective agonist, on caerulein-induced AP in mice. AP was induced by giving eight intraperitoneal injections of caerulein (50 µg/kg/h) at hourly intervals. SEW2871 was administered by gavage, at a dose of 20 mg/kg, at 0 h and 12 h after the first intraperitoneal injection of caerulein. The mice were sacrificed at 24 h. Severity of AP, serum amylase and lipase activity, levels of serum cytokines, pancreatic myeloperoxidase (MPO) activity, CD45 CD4 T lymphocytes in blood, CD4 T cell infiltration in the pancreas, and proinflammatory cytokine production were assessed. Furthermore, the expression of signal transducer and activator of transcription (STAT) 3 and phospho-STAT3 (p-STAT3) in the pancreas was also evaluated. The results revealed that the administration of SEW2871 ameliorated the severity of AP, by a reduction of serum pancreatic enzyme activity and levels of cytokines, decreased pancreatic MPO activity, depletion of CD4 CD45 T lymphocytes in the blood and a reduction of CD4 T cell infiltration in the pancreas. Furthermore, the expression of proinflammatory cytokines mRNA and p-STAT3 were also suppressed by SEW2871 treatment. These results suggest that SEW2871 treatment attenuates the severity of caerulein-induced AP in mice, which may provide a new therapeutic approach for AP therapy.

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A sphingosine-1-phosphate type 1 receptor agonist inhibits the early T-cell transient following renal ischemia–reperfusion injury

Cited by 68 publications

References 44 publications

Targeting sphingosine 1 phosphate receptor type 1 receptors in acute kidney injury

Targeting sphingosine 1 phosphate receptor type 1 receptors in acute kidney injury

Osteopontin Expressed in Tubular Epithelial Cells Regulates NK Cell-Mediated Kidney Ischemia Reperfusion Injury

SEW2871 Alleviates the Severity of Caerulein-Induced Acute Pancreatitis in Mice

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