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RIP1 kinase activity is critical for skin inflammation but not for viral propagation

Receptor interacting protein kinase 1 (RIP1) is a critical effector of inflammatory responses and cell death activation. Cell death pathways regulated by RIP1 include caspase‐dependent apoptosis and caspase‐independent necroptosis. The kinase activity of RIP1 has been associated with a number of inf...

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Autores principales: Webster, Joshua D., Kwon, Youngsu C., Park, Summer, Zhang, Hua, Corr, Nick, Ljumanovic, Nina, Adedeji, Adeyemi O., Varfolomeev, Eugene, Goncharov, Tatiana, Preston, Jessica, Santagostino, Sara F., Patel, Snahel, Xu, Min, Maher, Jonathan, McKenzie, Brent S., Vucic, Domagoj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317411/
https://www.ncbi.nlm.nih.gov/pubmed/31985117
http://dx.doi.org/10.1002/JLB.3MA1219-398R
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author Webster, Joshua D.
Kwon, Youngsu C.
Park, Summer
Zhang, Hua
Corr, Nick
Ljumanovic, Nina
Adedeji, Adeyemi O.
Varfolomeev, Eugene
Goncharov, Tatiana
Preston, Jessica
Santagostino, Sara F.
Patel, Snahel
Xu, Min
Maher, Jonathan
McKenzie, Brent S.
Vucic, Domagoj
author_facet Webster, Joshua D.
Kwon, Youngsu C.
Park, Summer
Zhang, Hua
Corr, Nick
Ljumanovic, Nina
Adedeji, Adeyemi O.
Varfolomeev, Eugene
Goncharov, Tatiana
Preston, Jessica
Santagostino, Sara F.
Patel, Snahel
Xu, Min
Maher, Jonathan
McKenzie, Brent S.
Vucic, Domagoj
author_sort Webster, Joshua D.
collection PubMed
description Receptor interacting protein kinase 1 (RIP1) is a critical effector of inflammatory responses and cell death activation. Cell death pathways regulated by RIP1 include caspase‐dependent apoptosis and caspase‐independent necroptosis. The kinase activity of RIP1 has been associated with a number of inflammatory, neurodegenerative, and oncogenic diseases. In this study, we use the RIP1 kinase inhibitor GNE684 to demonstrate that RIP1 inhibition can effectively block skin inflammation and immune cell infiltrates in livers of Sharpin mutant (Cpdm; chronic proliferative dermatitis) mice in an interventional setting, after disease onset. On the other hand, genetic inactivation of RIP1 (RIP1 KD) or ablation of RIP3 (RIP3 KO) or MLKL (MLKL KO) did not affect testicular pathology of aging male mice. Likewise, infection with vaccinia virus or with mouse gammaherpesvirus MHV68 resulted in similar viral clearance in wild‐type, RIP1 KD, and RIP3 KO mice. In summary, this study highlights the benefits of inhibiting RIP1 in skin inflammation, as opposed to its lack of relevance for testicular longevity and the response to certain viral infections.
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spelling pubmed-73174112020-06-30 RIP1 kinase activity is critical for skin inflammation but not for viral propagation Webster, Joshua D. Kwon, Youngsu C. Park, Summer Zhang, Hua Corr, Nick Ljumanovic, Nina Adedeji, Adeyemi O. Varfolomeev, Eugene Goncharov, Tatiana Preston, Jessica Santagostino, Sara F. Patel, Snahel Xu, Min Maher, Jonathan McKenzie, Brent S. Vucic, Domagoj J Leukoc Biol 17th International TNF Superfamily Conference 2019 Receptor interacting protein kinase 1 (RIP1) is a critical effector of inflammatory responses and cell death activation. Cell death pathways regulated by RIP1 include caspase‐dependent apoptosis and caspase‐independent necroptosis. The kinase activity of RIP1 has been associated with a number of inflammatory, neurodegenerative, and oncogenic diseases. In this study, we use the RIP1 kinase inhibitor GNE684 to demonstrate that RIP1 inhibition can effectively block skin inflammation and immune cell infiltrates in livers of Sharpin mutant (Cpdm; chronic proliferative dermatitis) mice in an interventional setting, after disease onset. On the other hand, genetic inactivation of RIP1 (RIP1 KD) or ablation of RIP3 (RIP3 KO) or MLKL (MLKL KO) did not affect testicular pathology of aging male mice. Likewise, infection with vaccinia virus or with mouse gammaherpesvirus MHV68 resulted in similar viral clearance in wild‐type, RIP1 KD, and RIP3 KO mice. In summary, this study highlights the benefits of inhibiting RIP1 in skin inflammation, as opposed to its lack of relevance for testicular longevity and the response to certain viral infections. John Wiley and Sons Inc. 2020-01-27 2020-06 /pmc/articles/PMC7317411/ /pubmed/31985117 http://dx.doi.org/10.1002/JLB.3MA1219-398R Text en © 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle 17th International TNF Superfamily Conference 2019
Webster, Joshua D.
Kwon, Youngsu C.
Park, Summer
Zhang, Hua
Corr, Nick
Ljumanovic, Nina
Adedeji, Adeyemi O.
Varfolomeev, Eugene
Goncharov, Tatiana
Preston, Jessica
Santagostino, Sara F.
Patel, Snahel
Xu, Min
Maher, Jonathan
McKenzie, Brent S.
Vucic, Domagoj
RIP1 kinase activity is critical for skin inflammation but not for viral propagation
title RIP1 kinase activity is critical for skin inflammation but not for viral propagation
title_full RIP1 kinase activity is critical for skin inflammation but not for viral propagation
title_fullStr RIP1 kinase activity is critical for skin inflammation but not for viral propagation
title_full_unstemmed RIP1 kinase activity is critical for skin inflammation but not for viral propagation
title_short RIP1 kinase activity is critical for skin inflammation but not for viral propagation
title_sort rip1 kinase activity is critical for skin inflammation but not for viral propagation
topic 17th International TNF Superfamily Conference 2019
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317411/
https://www.ncbi.nlm.nih.gov/pubmed/31985117
http://dx.doi.org/10.1002/JLB.3MA1219-398R
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