Inhibition of CD26/DPP IV attenuates ischemia/reperfusion injury in orthotopic mouse lung transplants: The pivotal role of vasoactive intestinal peptide

Jungraithmayr, Wolfgang; Meester, Ingrid De; Matheeussen, Veerle; İnci, İlhan; Augustyns, Koen; Scharpé, Simon; Weder, Walter; Korom, Stephan

doi:10.1016/j.peptides.2009.12.012

Cited by 40 publications

(21 citation statements)

References 28 publications

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“…Our group reported that alogliptin inhibited toll-like receptor (TLR4)-mediated extracellular signal-regulated kinase (ERK) signaling activation and ERK-dependent MMP expression by mononuclear cells (4). Furthermore, it has been reported that treatment of orthotopic mouse lung transplants with DPP-4 inhibitor resulted in significant improvement of gas exchange, less lipid oxidation, preservation of parenchymal ultrastructure, reduced neutrophil infiltration, and reduced myeloperoxidase expression, leading to a less ischemia/reperfusion injury and better lung function and structure integrity (5). …”

Section: Discussionmentioning

confidence: 99%

“…Our group found that alogliptin inhibited the expression of matrix metalloproteinases (MMPs), a group of powerful proteinases involved in the tissue degradation and tissue remodeling in inflammatory diseases (4). Furthermore, Jungraithmayr et al reported that DPP-4 inhibitor attenuated ischemia/reperfusion injury in mouse lung transplants (5). Given that DPP-4 is identical to CD26 (6), a cell surface glycoprotein with multiple functions in T cell activation, DNA synthesis, cell proliferation, cytokine production and signaling activation (7-9), it is likely that inhibition of DPP-4 (CD26) modulates inflammatory processes.…”

Section: Introductionmentioning

confidence: 99%

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DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice

Schuyler

et al. 2011

Journal of Cardiovascular Pharmacology

146

103

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Dipeptidyl peptidase-4 (DPP-4 or CD26) inhibitors, a new class of anti-diabetic compounds, are effective in treatment of hyperglycemia. Since atherosclerosis-related cardiovascular diseases are the major complications of diabetes, it is important to determine the effect of DPP-4 inhibitors on atherosclerosis. In this study, nondiabetic and diabetic apolipoprotein E (apoE)-deficient mice were treated with DPP-4 inhibitor alogliptin for 24 weeks and atherosclerotic lesions in aortic origins were examined. Results showed that diabetes significantly increased atherosclerotic lesions, but alogliptin treatment reduced atherosclerotic lesions in diabetic mice. Metabolic studies showed that diabetes increased plasma glucose and alogliptin treatment reduced glucose. Furthermore, immunohistochemistry study showed that diabetes increased IL-6 and IL-1β protein expression in atherosclerotic plaques, but alogliptin treatment attenuated diabetes-augmented IL-6 and IL-1β expression. In consistence with the observations from the mouse models, our in vitro studies showed that alogliptin inhibited toll-like receptor (TLR)4-mediated upregulation of IL-6, IL-1β, and other proinflammatory cytokines by mononuclear cells. Taken together, our findings showed that alogliptin inhibited atherosclerosis in diabetic apoE-deficient mice and the actions of alogliptin on both glucose and inflammation may contribute to the inhibition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice

Schuyler

et al. 2011

Journal of Cardiovascular Pharmacology

146

103

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“…The orthotopic mouse LTx model has so far mainly been used in the study of acute rejection [15] and ischemia-reperfusion injury [16]; [17], both risk factors for BOS. Since BOS is the main cause of late mortality/morbidity after LTx, the development of a new BOS model starting from orthotopic LTx is a logical step.…”

Section: Discussionmentioning

confidence: 99%

Chronic Rejection Pathology after Orthotopic Lung Transplantation in Mice: The Development of a Murine BOS Model and Its Drawbacks

et al. 2012

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Almost all animal models for chronic rejection (CR) after lung transplantation (LTx) fail to resemble the human situation. It was our attempt to develop a representative model of CR in mice. Orthotopic LTx was performed in allografts receiving daily immunosuppression with steroids and cyclosporine. Controls included isografts and mice only undergoing thoracotomy (SHAM). Allografts were sacrificed 2, 4, 6, 8, 10 or 12 weeks after LTx. Pulmonary function was measured repeatedly in the 12w allografts, isografts and SHAM mice. Histologically, all allografts demonstrated acute rejection (AR) around the blood vessels and airways two weeks after LTx. This decreased to 50–75% up to 10 weeks and was absent after 12 weeks. Obliterative bronchiolitis (OB) lesions were observed in 25–50% of the mice from 4–12 weeks. Isografts and lungs of SHAM mice were normal after 12 weeks. Pulmonary function measurements showed a decline in FEV0.1, TLC and compliance in the allografts postoperatively (2 weeks) with a slow recovery over time. After this initial decline, lung function of allografts increased more than in isografts and SHAM mice indicating that pulmonary function measurement is not a good tool to diagnose CR in a mouse. We conclude that a true model for CR, with clear OB lesions in about one third of the animals, but without a decline in lung function, is possible. This model is an important step forward in the development of an ideal model for CR which will open new perspectives in unraveling CR pathogenesis and exploring new treatment options.

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“…13 Studying mouse models offers various advantages, for instance, the possibility to specifically investigate the pathological processes leading to I/R injury 14 or the outcome of experimental treatments. 15 To this end, a noninvasive assessment via imaging would be advantageous and might help to improve I/R injury evaluation after lung transplantations.…”

Section: Assessing Lung Transplantation Ischemia-reperfusion Injury Bmentioning

confidence: 99%

Assessing Lung Transplantation Ischemia-Reperfusion Injury by Microcomputed Tomography and Ultrashort Echo-Time Magnetic Resonance Imaging in a Mouse Model

Wurnig¹,

Tsushima²,

Weiger³

et al. 2014

Investigative Radiology

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PURPOSE: Ischemia-reperfusion injury (I/R) is a common early complication after lung transplantation. The purpose of this study was to compare ultrashort echo-time (UTE) sequences in magnetic resonance imaging (MRI) with a microcomputed tomography (micro-CT) reference standard for detection of I/R injury in a lung transplantation mouse model. MATERIALS AND METHODS: Six mice (C57BL/6) underwent orthotopic lung transplantation using donor grafts that were exposed to 6-hour cold ischemia. Imaging was performed within 24 hours after the transplantation with high-resolution micro-CT (tube voltage, 50 kV; current, 500 mA; aluminum filter, 0. (35); mean (SD) S0 value, 2310 (300); and mean (SD) T2*, 4550 (3230) s for the transplanted left lung. Slight infiltration could be better discriminated with micro-CT, whereas, in strong infiltration, a better contrast was provided by UTE MRI. The area under the curve values resulting from the receiver operating characteristic curve analysis were 0.99 for HU density, 0.89 for S0, 0.96 for T2*, and 0.98 for the combination of S0 and T2*. CONCLUSIONS: Results show that MRI of the lung has a similar diagnostic power compared with that of micro-CT regarding the detection of I/R injury after experimental lung transplantation. Both modalities provide complementary information in the assessment of dense and slight infiltration in the early phase after lung transplantation. Therefore, UTE MRI seems to be a promising addition to computed tomographic imaging in the assessment of I/R injury after lung transplantation.

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Inhibition of CD26/DPP IV attenuates ischemia/reperfusion injury in orthotopic mouse lung transplants: The pivotal role of vasoactive intestinal peptide

Cited by 40 publications

References 28 publications

DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice

DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice

Chronic Rejection Pathology after Orthotopic Lung Transplantation in Mice: The Development of a Murine BOS Model and Its Drawbacks

Assessing Lung Transplantation Ischemia-Reperfusion Injury by Microcomputed Tomography and Ultrashort Echo-Time Magnetic Resonance Imaging in a Mouse Model

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