Decreased renal ischemia–reperfusion injury by IL-16 inactivation

Wang, S.; Diao, Hong; Guan, Qiunong; Cruikshank, William W.; Delovitch, Terry L.; Jevnikar, Anthony M.; Du, Caigan

doi:10.1038/sj.ki.5002692

Cited by 52 publications

(26 citation statements)

References 55 publications

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“…IL-16 is a T-cell chemoattractant produced by leukocytes. Wang et al reported that IL-16 was a critical factor in the development of inflammation-mediated renal injury and may be a therapeutic target for prevention of ischemia-reperfusion injury of the kidney (Wang et al, 2008). A plethora of studies have also implicated IL-16 in exacerbation of infectious, immune-mediated, and autoimmune inflammatory disorders, including atopic dermatitis, irritable bowel syndrome, systemic lupus erythematosus, neurodegenerative disorders, and viral infections (Glass et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Critical role of PBEF expression in pulmonary cell inflammation and permeability

Liu

Cepeda

et al. 2009

Cell Biology International

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Previous studies in our lab have identified Pre-B-cell colony enhancing factor as a novel biomarker in acute lung injury. This study continues to elucidate the underlying molecular mechanism of Pre-B-cell colony enhancing factor (PBEF) in the pathogenesis of acute lung injury in pulmonary cell culture models. Our results revealed that IL-1β induced PBEF expression in pulmonary vascular endothelial cells at the transcriptional level and a -1535 T-variant in the human PBEF gene promoter significantly attenuated its binding to an IL-1β induced unknown transcription factor. This may underlie the reduced expression of PBEF and thus the less susceptibility to acute lung injury in those -1535T carriers. Furthermore, overexpression of PBEF significantly augmented IL-8 secretion and mRNA expression by more than 6 fold and 2 fold in A549 cells and HPAEC, respectively. It also significantly augmented IL-1β mediated cell permeability by 44% in A549 cells and 65% in endothelial cells. The knockdown of PBEF expression significantly inhibited IL-1β-stimulated IL-8 secretion and mRNA level by 60% and 70%, respectively; and the knockdown of PBEF expression also significantly attenuated IL-1β-induced cell permeability by 29% in epithelial cells and 24% in endothelial cells. PBEF expression also affected the expression of two other inflammatory cytokines (IL-16 and CCR3 genes). These results suggest that PBEF is critically involved in pulmonary vascular and epithelial inflammation and permeability, which are hallmark features in the pathogenesis of acute lung injury. This study lend further support that PBEF is a potential new target in acute lung injury.

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Section: Discussionmentioning

confidence: 99%

Critical role of PBEF expression in pulmonary cell inflammation and permeability

Liu

Cepeda

et al. 2009

Cell Biology International

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“…Studies of models of acute inflammation have established IL-8 as a key mediator in neutrophil-mediated acute inflammation (31). Wang et al reported that IL-16 was a critical factor in the development of inflammation-mediated renal injury and may be a therapeutic target for prevention of ischemia-reperfusion injury of the kidney (32). Animal studies suggest that CCR3 is a prominent mediator of allergic responses and that antagonizing the receptor will lead to a reduction in airway inflammation (33).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Inflammatory Cytokine Expression in Pulmonary Epithelial Cells by Pre-B-cell Colony-enhancing Factor via a Nonenzymatic and AP-1-dependent Mechanism

Liu

Cepeda

et al. 2009

Journal of Biological Chemistry

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Although our previous studies found Pre-B-cell colony-enhancing factor (PBEF) as a highly up-regulated gene in acute lung injury that could stimulate expressions of other inflammatory cytokines, the underlying molecular mechanisms remain to be fully elucidated. Growing evidence indicates that PBEF is a nicotinamide phosphoribosyltransferase involved in the mammalian salvage pathway of NAD synthesis. This study was designed to determine whether the effect of PBEF to stimulate expressions of inflammatory cytokines depends on its enzymatic activity. We prepared two human PBEF mutant (H247E and H247A) recombinant proteins and overexpressing constructs for their overexpressions in A549 cells and confirmed that enzymatic activities of both mutants were nearly or completely abolished. Two mutants stimulated interleukin-8 (IL-8) expression at both the mRNA level and protein level just as equally effective as the wild-type PBEF did. These effects were due to the increased transcription, not the mRNA stability, of the IL-8 gene. Reporter gene assays and gel shift experiments indicated that AP-1 transcription factor is required to mediate these effects. SB203580, a p38 MAPK pathway inhibitor, and JNK inhibitor 1 can attenuate these effects. Both PBEF mutants similarly stimulated the expression of two other inflammatory cytokines: IL-16 and CCR3. These results indicate that PBEF stimulated expression of IL-8, IL-16, and CCR3 via its non-enzymatic activity. This effect is AP-1-dependent, in part via the p38 MAPK pathway and the JNK pathway. This finding reveals a new insight, which may manifest a novel role of PBEF in the pathogenesis of acute lung injury and other inflammatory disorders. Acute lung injury (ALI)2 and its more severe form, acute respiratory distress syndrome (ARDS), are characterized by inflammation of the lung parenchyma leading to impaired gas exchange with concomitant systemic release of inflammatory mediators causing inflammation, hypoxemia, and frequently resulting in multiple organ failure (1, 2). Although ALI/ARDS was first described in 1967 by Ashbaugh et al. (3), its mortality and morbidity remain high (4). More studies are warranted to elucidate its molecular pathogenesis and to identify new diagnostic and therapeutic targets to ALI/ARDS.In our previous study on animal models of ALI and human patients with ARDS, we identified pre-B-cell colony-enhancing factor (PBEF) as a biochemical and genetic marker in ALI (5). Our findings were confirmed and extended in a separate and larger population (Ͼ1000 patients) by Bajwa et al. (6). In further studies, we demonstrated that overexpression of PBEF can augment the expression of inflammatory cytokines and dysregulate pulmonary cell barrier function, whereas inhibition of PBEF expression by its cognate small interference RNA has the opposite effects (7-9). PBEF has been confirmed as a nicotinamide phosphoribosyltransferase (Nampt) involved in the mammalian salvage pathway of NAD synthesis (10,11). Whether the enzymatic activity of PBEF is involved in its effe...

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“…The T cells have been attributed to play a significant role in the pathogenesis of renal IRI [50,51,52]. Studies have shown both direct and indirect blockade of T cells reduced renal functional and structural injury in murine renal IRI models [51,52,53]. In athymic nu/nu mice (T-cell knockout mouse strain) subjected to IRI, not only protection from initial renal injury but also an adoptive T-cell transfer into these mice restored the renal injury [54].…”

Section: Role Of Thymoglobulin In Ischemia-reperfusion Injurymentioning

confidence: 99%

Thymoglobulin and Its Use in Renal Transplantation: A Review

2013

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Thymoglobulin (Thymoglobulin®; Genzyme, Cambridge, Mass., USA) is a polyclonal antibody which has been used in the field of transplantation over the last four decades. With an initial hesitancy, it is widely used now in the prevention and treatment of rejection following renal transplantation. Thymoglobulin's lack of nephrotoxic properties (unlike calcineurin inhibitors) may potentiate it to be a very useful induction therapy during the early days following transplantation, particularly in a donation after circulatory death programme. More recently its role in conjunction with inhibitors of terminal complement activation has been shown to be beneficial in cross-match-positive transplantation. This review article consolidates up-to-date available evidence to address the therapeutic role of thymoglobulin in immunological tolerance, ischemia perfusion, live donor transplantation, delayed graft function, prevention and treatment of rejection, graft survival and post-transplant lymphoproliferative disorder following renal transplantation.

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Decreased renal ischemia–reperfusion injury by IL-16 inactivation

Cited by 52 publications

References 55 publications

Critical role of PBEF expression in pulmonary cell inflammation and permeability

Critical role of PBEF expression in pulmonary cell inflammation and permeability

Regulation of Inflammatory Cytokine Expression in Pulmonary Epithelial Cells by Pre-B-cell Colony-enhancing Factor via a Nonenzymatic and AP-1-dependent Mechanism

Thymoglobulin and Its Use in Renal Transplantation: A Review

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