Suppression of acute rejection by administration of prostaglandin E2 receptor subtype 4 agonist in rat organ transplantation models

Okamoto, Tatsuya; Okamoto, Shinya; Fujimoto, Yasuhiro; Tabata, Yasuhiko; Üemoto, Shinji

doi:10.1016/j.jss.2013.01.039

Cited by 6 publications

(3 citation statements)

References 20 publications

(17 reference statements)

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“…EP4 agonist was more effective than the EP2 agonist to inhibit acute allograft rejection, suggesting more important role of EP4. Some exciting data have emerged concerning the EP4 selective agonist as a novel agent to protect both posttransplantation inflammatory and alloimmune responses [42,[46][47][48]. However, in our study we were not able to assess the importance of EP4 receptor in progression of renal dysfunction in kidney allografts with findings of subclinical or clinical inflammation as the PTGER4 gene was not included in the evaluated gene set.…”

Section: Discussionmentioning

confidence: 92%

Molecular Patterns of Subclinical and Clinical Rejection of Kidney Allograft: Quantity Matters

Wohlfahrtová¹,

Tycova²,

Honsová

et al. 2015

Kidney Blood Press Res

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Background/Aims: Subclinical rejection diagnosed from protocol biopsies is thought to be a risk factor of long- term allograft dysfunction. The reason why in some patients subclinical rejection does not represent risk for progression is not fully understood. Methods: The intragraft expression of 376 target genes involved in chemokine defense, apoptosis, inflammation, tolerance and TGF-β signalling pathways was measured using quantitative real-time RT-PCR (2^-∆∆^Ct) method in subclinical inflammation (SCI, n=10), clinical inflammation in acute T-cell mediated rejection (CI, n=10) and no rejection samples (n=9). Results: Clinical inflammation group showed a increased expression of genes for chemotaxis mediating cytokines (CCL1, CCL17, CCL24, CCL25, CCL26), cytokine receptors (CCR1, CCRL2, IL1RAPL2, CXCR5), proinflammatory cytokines (IL12A, LTA), inflammatory mediator (PTAFR), complement protein C3, executioner protein of apoptosis (CASP7), growth factor (TGFA), colony stimulating factor (CSF-2), proteins involved in dendritic cells differentiation and interaction (CD209, LAMP3), regulation of immune response (LILRB2, LILBRB4). The quantitative difference in transcripts signature between SCI and CI is consistent with stronger proinflammatory setting of CI. Prostaglandin E2 receptor gene expression was independently associated with lower risk of further graft function deterioration (OR 0.11, CI 0.01-0.78, p<0.0001). Conclusion: Subclinical acute kidney inflammation has transcriptional profile of immune injury of lower extend compared to clinical acute inflammation.

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Section: Discussionmentioning

confidence: 92%

Molecular Patterns of Subclinical and Clinical Rejection of Kidney Allograft: Quantity Matters

Wohlfahrtová¹,

Tycova²,

Honsová

et al. 2015

Kidney Blood Press Res

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“…The only method that has been shown to completely prevent the FBR is the use of local delivery of anti-inflammatory agents which prevent infiltration and further attraction of inflammatory cells [25][26][27][28][29][30][31][32]. Systemic administration of anti-inflammatory agents and immuno-suppressants is regularly used to prevent organ rejection [33][34][35][36][37][38][39][40][41] but it is not a desirable approach for medical devices and implantable biomaterials due to the high risk-to-benefit ratio.…”

Section: Introductionmentioning

confidence: 99%

Prevention of foreign body reaction in a pre-clinical large animal model

Kastellorizios

Papadimitrakopoulos

Burgess

2015

Journal of Controlled Release

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“…The HITx has been used to establish the proof of concept of different immune modulation strategies to avoid rejection, as well as to study immunological reactions involved in graft rejection. [6][7][8][9][10] We here report the use of a HITx model to study the impact of the initial stages of acute cellular rejection (ACR) on graft functional features, such as absorptive capacity, barrier function, and motility. We analyzed the kinetics of these variations in the context of the characterization of clinical and molecular changes associated with the ACR process.…”

mentioning

confidence: 99%

Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model

et al. 2017

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Background. Intestinal transplantation (ITx) faces many challenges due to the complexity of surgery and to the multiple immunological reactions that lead to the necessity of rigorous follow-up for early detection of acute cellular rejection (ACR). Our aim was to determine the kinetics of ACR using an experimental ITx model, with emphasis in the characterization of the process using different approaches, including the use of functional assays of absorptive and barrier function. Methods. ITx in rats conducting serial sampling was performed. Clinical monitoring, graft histology, proinflammatory gene expression, and nitrosative stress determination were performed. Also, glucose absorption, barrier function using ovalbumin translocation, and contractile function were analyzed. Results. The model used reproduced the different stages of ACR. Allogeneic ITx recipients showed signs of rejection from postoperative day (POD) 5, with increasing severity until 12 POD. Histological evaluation showed mild rejection in early sampling and severe rejection at late stages, with alterations in all graft layers. IL-6, CXCL 10, IFNg, and nitrite plasmas levels showed behavior coincident with histopathology. Remarkably, allogeneic grafts showed a marked alteration of glucose absorptive capacity from POD 5 that was sustained until endpoint. Coincidently, barrier function alteration was evidenced by luminal ovalbumin translocation to serum. Contractile function was progressively impaired along ACR. Conclusions. Glucose absorption and barrier function are altered at early stages of ACR when histological alterations or gene expression changes were much subtle. This observation may provide simple evaluation tools that could be eventually translated to the clinics to contribute to early ACR diagnosis.

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Suppression of acute rejection by administration of prostaglandin E2 receptor subtype 4 agonist in rat organ transplantation models

Abstract: These results suggest that selective EP4 agonists represent a novel class of immune-modulator drugs that could be useful for the management of acute allogeneic rejection.

Cited by 6 publications

References 20 publications

Molecular Patterns of Subclinical and Clinical Rejection of Kidney Allograft: Quantity Matters

Molecular Patterns of Subclinical and Clinical Rejection of Kidney Allograft: Quantity Matters

Prevention of foreign body reaction in a pre-clinical large animal model

Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model

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