PortalPublikationenA novel JAK3 inhibitor, R348, attenuates chronic airway allo...

A novel JAK3 inhibitor, R348, attenuates chronic airway allograft rejection

Standard

A novel JAK3 inhibitor, R348, attenuates chronic airway allograft rejection. / Velotta, Jeffrey B; Deuse, Tobias; Haddad, Munif; Masuda, Esteban; Park, Gary; Carroll, David; Taylor, Vanessa; Robbins, Robert C; Schrepfer, Sonja.

in: TRANSPLANTATION, Jahrgang 87, Nr. 5, 15.03.2009, S. 653-659.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Velotta, JB, Deuse, T, Haddad, M, Masuda, E, Park, G, Carroll, D, Taylor, V, Robbins, RC & Schrepfer, S 2009, 'A novel JAK3 inhibitor, R348, attenuates chronic airway allograft rejection', TRANSPLANTATION, Jg. 87, Nr. 5, S. 653-659. https://doi.org/10.1097/TP.0b013e318196110f

APA

Velotta, J. B., Deuse, T., Haddad, M., Masuda, E., Park, G., Carroll, D., Taylor, V., Robbins, R. C., & Schrepfer, S. (2009). A novel JAK3 inhibitor, R348, attenuates chronic airway allograft rejection. TRANSPLANTATION, 87(5), 653-659. https://doi.org/10.1097/TP.0b013e318196110f

Vancouver

Velotta JB, Deuse T, Haddad M, Masuda E, Park G, Carroll D et al. A novel JAK3 inhibitor, R348, attenuates chronic airway allograft rejection. TRANSPLANTATION. 2009 Mär 15;87(5):653-659. https://doi.org/10.1097/TP.0b013e318196110f

Bibtex

@article{ba5e8b2e45cf4559ad612ec080e0faee,
title = "A novel JAK3 inhibitor, R348, attenuates chronic airway allograft rejection",
abstract = "BACKGROUND: This study aimed at investigating the role of a novel JAK3 inhibitor, R348, in the prevention of chronic airway allograft rejection.METHODS: The heterotopic rat trachea transplant model was used. Recipients were treated daily with R348 (10, 20, 40, 80 mg/kg) or rapamycin (0.75 or 3 mg/kg). Blood levels of R348 and of its active metabolite R333 were measured. Grafts were harvested after 28 days to analyze epithelial morphology, mononuclear infiltration, and luminal obliteration. Plasma levels of circulating donor strain-reactive IgG antibodies were quantified.RESULTS: R348 was well tolerated at up to 40 mg/kg, but was toxic at 80 mg/kg. Blood levels of R333 at 2 and 24 hr were consistently 10 to 15 times higher than those of R348. Airway luminal obliteration after 28 days was significantly inhibited by R348 at 40 mg/kg (20.6%+/-13.2%, P<0.05) and 80 mg/kg (15.7%+/-7.6%, P<0.05) and by rapamycin at 3 mg/kg (11.6%+/-6.7% P<0.001) versus untreated controls (100%). R348 is more than or equal to 40 mg/kg but neither dose of rapamycin preserved the physiologic epithelial coverage with its prominent goblet cells population (8.8+/-1.5 goblet cells/microm circumference in syngeneic grafts and 8.0+/-0.9 and 4.3+/-1.2 with R348 80 mg/kg and 40 mg/kg, respectively). Peritracheal graft mononuclear infiltration was most effectively suppressed by R348 is more than or equal to 40 mg/kg (P<0.05) and rapamycin 3 mg/kg (P<0.01). Donor strain-reactive IgG antibodies were significantly decreased by R348 is more than or equal to 40 mg/kg (PCONCLUSIONS: R348 is an effective drug, and it is expected to be introduced into clinical transplant pharmacology soon.",
keywords = "Animals, Chronic Disease, Enzyme Inhibitors/therapeutic use, Graft Rejection/prevention & control, Janus Kinase 3/antagonists & inhibitors, Male, Rats, Rats, Inbred BN, Rats, Inbred Lew, Respiratory Mucosa/cytology, Sirolimus/therapeutic use, Transplantation, Homologous",
author = "Velotta, {Jeffrey B} and Tobias Deuse and Munif Haddad and Esteban Masuda and Gary Park and David Carroll and Vanessa Taylor and Robbins, {Robert C} and Sonja Schrepfer",
year = "2009",
month = mar,
day = "15",
doi = "10.1097/TP.0b013e318196110f",
language = "English",
volume = "87",
pages = "653--659",
journal = "TRANSPLANTATION",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

RIS

TY - JOUR

T1 - A novel JAK3 inhibitor, R348, attenuates chronic airway allograft rejection

AU - Velotta, Jeffrey B

AU - Deuse, Tobias

AU - Haddad, Munif

AU - Masuda, Esteban

AU - Park, Gary

AU - Carroll, David

AU - Taylor, Vanessa

AU - Robbins, Robert C

AU - Schrepfer, Sonja

PY - 2009/3/15

Y1 - 2009/3/15

N2 - BACKGROUND: This study aimed at investigating the role of a novel JAK3 inhibitor, R348, in the prevention of chronic airway allograft rejection.METHODS: The heterotopic rat trachea transplant model was used. Recipients were treated daily with R348 (10, 20, 40, 80 mg/kg) or rapamycin (0.75 or 3 mg/kg). Blood levels of R348 and of its active metabolite R333 were measured. Grafts were harvested after 28 days to analyze epithelial morphology, mononuclear infiltration, and luminal obliteration. Plasma levels of circulating donor strain-reactive IgG antibodies were quantified.RESULTS: R348 was well tolerated at up to 40 mg/kg, but was toxic at 80 mg/kg. Blood levels of R333 at 2 and 24 hr were consistently 10 to 15 times higher than those of R348. Airway luminal obliteration after 28 days was significantly inhibited by R348 at 40 mg/kg (20.6%+/-13.2%, P<0.05) and 80 mg/kg (15.7%+/-7.6%, P<0.05) and by rapamycin at 3 mg/kg (11.6%+/-6.7% P<0.001) versus untreated controls (100%). R348 is more than or equal to 40 mg/kg but neither dose of rapamycin preserved the physiologic epithelial coverage with its prominent goblet cells population (8.8+/-1.5 goblet cells/microm circumference in syngeneic grafts and 8.0+/-0.9 and 4.3+/-1.2 with R348 80 mg/kg and 40 mg/kg, respectively). Peritracheal graft mononuclear infiltration was most effectively suppressed by R348 is more than or equal to 40 mg/kg (P<0.05) and rapamycin 3 mg/kg (P<0.01). Donor strain-reactive IgG antibodies were significantly decreased by R348 is more than or equal to 40 mg/kg (PCONCLUSIONS: R348 is an effective drug, and it is expected to be introduced into clinical transplant pharmacology soon.

AB - BACKGROUND: This study aimed at investigating the role of a novel JAK3 inhibitor, R348, in the prevention of chronic airway allograft rejection.METHODS: The heterotopic rat trachea transplant model was used. Recipients were treated daily with R348 (10, 20, 40, 80 mg/kg) or rapamycin (0.75 or 3 mg/kg). Blood levels of R348 and of its active metabolite R333 were measured. Grafts were harvested after 28 days to analyze epithelial morphology, mononuclear infiltration, and luminal obliteration. Plasma levels of circulating donor strain-reactive IgG antibodies were quantified.RESULTS: R348 was well tolerated at up to 40 mg/kg, but was toxic at 80 mg/kg. Blood levels of R333 at 2 and 24 hr were consistently 10 to 15 times higher than those of R348. Airway luminal obliteration after 28 days was significantly inhibited by R348 at 40 mg/kg (20.6%+/-13.2%, P<0.05) and 80 mg/kg (15.7%+/-7.6%, P<0.05) and by rapamycin at 3 mg/kg (11.6%+/-6.7% P<0.001) versus untreated controls (100%). R348 is more than or equal to 40 mg/kg but neither dose of rapamycin preserved the physiologic epithelial coverage with its prominent goblet cells population (8.8+/-1.5 goblet cells/microm circumference in syngeneic grafts and 8.0+/-0.9 and 4.3+/-1.2 with R348 80 mg/kg and 40 mg/kg, respectively). Peritracheal graft mononuclear infiltration was most effectively suppressed by R348 is more than or equal to 40 mg/kg (P<0.05) and rapamycin 3 mg/kg (P<0.01). Donor strain-reactive IgG antibodies were significantly decreased by R348 is more than or equal to 40 mg/kg (PCONCLUSIONS: R348 is an effective drug, and it is expected to be introduced into clinical transplant pharmacology soon.

KW - Animals

KW - Chronic Disease

KW - Enzyme Inhibitors/therapeutic use

KW - Graft Rejection/prevention & control

KW - Janus Kinase 3/antagonists & inhibitors

KW - Male

KW - Rats

KW - Rats, Inbred BN

KW - Rats, Inbred Lew

KW - Respiratory Mucosa/cytology

KW - Sirolimus/therapeutic use

KW - Transplantation, Homologous

U2 - 10.1097/TP.0b013e318196110f

DO - 10.1097/TP.0b013e318196110f

M3 - SCORING: Journal article

C2 - 19295308

VL - 87

SP - 653

EP - 659

JO - TRANSPLANTATION

JF - TRANSPLANTATION

SN - 0041-1337

IS - 5

ER -