Gene therapy with adenovirus‐delivered indoleamine 2,3‐dioxygenase improves renal function and morphology following allogeneic kidney transplantation in rat

Vavrincova-Yaghi, Diana; Deelman, Leo E.; Goor, Harry van; Seelen, Marc A.; Kema, Ido P.; Oosten, Annemieke Smit-van; Zeeuw, Dick de; Henning, Robert H.; Sandovici, Maria

doi:10.1002/jgm.1584

Cited by 23 publications

(19 citation statements)

References 55 publications

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“…Induction of IL-17 expression has been described in studies using recombinant HAdV-based vectors in mice or rats (Hou et al, 2013; Vavrincova-Yaghi et al, 2011), but no data exist that describe IL-17 induction in the context of respiratory infection by an adenovirus in its natural host. Our results clearly demonstrate robust induction of IL-17A mRNA and protein in the lungs of mice infected with MAV-1.…”

Section: Discussionmentioning

confidence: 99%

IL-17 contributes to neutrophil recruitment but not to control of viral replication during acute mouse adenovirus type 1 respiratory infection

et al. 2014

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IL-17-producing CD4+ helper T cells (Th17 cells) promote inflammatory responses to many pathogens. We used mouse adenovirus type 1 (MAV-1) to determine contributions of IL-17 to adenovirus pathogenesis. MAV-1 infection of C57BL/6 mice upregulated lung expression of IL-17 and the Th17-associated factors IL-23 and RORγt. Only CD4+ T cells were associated with virus-specific IL-17 production. Fewer neutrophils were recruited to airways of IL-17−/− mice following MAV-1 infection, but there were no other differences in pulmonary inflammation between IL-17+/+ and IL-17−/− mice. Mice depleted of neutrophils using anti-Gr-1 antibody had greater lung viral loads than controls. Despite impaired neutrophil recruitment, there were no differences between IL-17+/+ and IL-17−/− mice in peak lung viral loads, clearance of virus from the lungs, or establishment of protective immunity. We demonstrate robust Th17 responses during MAV-1 respiratory infection, but these responses are not essential for control of virus infection or for virus-induced pulmonary inflammation.

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Section: Discussionmentioning

confidence: 99%

IL-17 contributes to neutrophil recruitment but not to control of viral replication during acute mouse adenovirus type 1 respiratory infection

et al. 2014

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“…We chose recombinant adeno-associated virus (rAAV) to deliver shRNA against rat STIM1 to rat kidney, because the in vivo rAAV/shRNA delivery system has been well developed in rats. [51][52][53][54] The rAAV-carried eGFP-tagged shRNA against rat STIM1 (rAAV-eGFP-shStim1) was administered to rats by tail vein injection. An rAAV1/2 encoding an eGFP-tagged scrambled shRNA served as a control.…”

Section: In Vivo Knockdown Of Stim1 In Mcs Increased Col IV Protein Ementioning

confidence: 99%

Store–Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein Expression

Wang

Davis

et al. 2015

Journal of the American Society of Nephrology

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Accumulation of extracellular matrix derived from glomerular mesangial cells is an early feature of diabetic nephropathy. Ca 2+ signals mediated by store-operated Ca 2+ channels regulate protein production in a variety of cell types. The aim of this study was to determine the effect of store-operated Ca 2+ channels in mesangial cells on extracellular matrix protein expression. In cultured human mesangial cells, activation of store-operated Ca 2+ channels by thapsigargin significantly decreased fibronectin protein expression and collagen IV mRNA expression in a dose-dependent manner. Conversely, inhibition of the channels by 2-aminoethyl diphenylborinate significantly increased the expression of fibronectin and collagen IV. Similarly, overexpression of stromal interacting molecule 1 reduced, but knockdown of calcium releaseactivated calcium channel protein 1 (Orai1) increased fibronectin protein expression. Furthermore, 2-aminoethyl diphenylborinate significantly augmented angiotensin II-induced fibronectin protein expression, whereas thapsigargin abrogated high glucose-and TGF-b1-stimulated matrix protein expression. In vivo knockdown of Orai1 in mesangial cells of mice using a targeted nanoparticle siRNA delivery system resulted in increased expression of glomerular fibronectin and collagen IV, and mice showed significant mesangial expansion compared with controls. Similarly, in vivo knockdown of stromal interacting molecule 1 in mesangial cells by recombinant adeno-associated virus-encoded shRNA markedly increased collagen IV protein expression in renal cortex and caused mesangial expansion in rats. These results suggest that store-operated Ca 2+ channels in mesangial cells negatively regulate extracellular matrix protein expression in the kidney, which may serve as an endogenous renoprotective mechanism in diabetes.

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“…Our study was based on the hypothesis that Tregs are also regulated by immunologically superior cells, such as antigen presenting cells producing interferon gamma, as shown in in vivo rodent transplant models. 12,13 Transplanted grafts can be recognized as nonself by host immunity, as can cancerous cells. Therefore, we hypothesize that the same mechanism occurs in tumor immunity for IPMNs.…”

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3-dioxygenase Affects the Aggressiveness of Intraductal Papillary Mucinous Neoplasms Through Foxp3+CD4+CD25+ T Cells in Peripheral Blood

Ikemoto

Shimada²,

Komatsu³

et al. 2013

Pancreas

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Gene therapy with adenovirus‐delivered indoleamine 2,3‐dioxygenase improves renal function and morphology following allogeneic kidney transplantation in rat

Abstract: RGD-AdTIDO therapy improves renal function and morphology in a clinically relevant model of acute rejection.

Cited by 23 publications

References 55 publications

IL-17 contributes to neutrophil recruitment but not to control of viral replication during acute mouse adenovirus type 1 respiratory infection

IL-17 contributes to neutrophil recruitment but not to control of viral replication during acute mouse adenovirus type 1 respiratory infection

Store–Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein Expression

Indoleamine 2,3-dioxygenase Affects the Aggressiveness of Intraductal Papillary Mucinous Neoplasms Through Foxp3+CD4+CD25+ T Cells in Peripheral Blood

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