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

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Tytuł:: RIP1 kinase activity is critical for skin inflammation but not for viral propagation.
Autorzy:: Webster JD; Departments of Pathology, Genentech, South San Francisco, California, USA.
Kwon YC; Translational Immunology, Genentech, South San Francisco, California, USA.
Park S; Translational Immunology, Genentech, South San Francisco, California, USA.
Zhang H; Translational Immunology, Genentech, South San Francisco, California, USA.
Corr N; Safety Assessment, Genentech, South San Francisco, California, USA.
Ljumanovic N; Safety Assessment, Genentech, South San Francisco, California, USA.
Adedeji AO; Safety Assessment, Genentech, South San Francisco, California, USA.
Varfolomeev E; Early Discovery Biochemistry, Genentech, South San Francisco, California, USA.
Goncharov T; Early Discovery Biochemistry, Genentech, South San Francisco, California, USA.
Preston J; Departments of Pathology, Genentech, South San Francisco, California, USA.
Santagostino SF; Safety Assessment, Genentech, South San Francisco, California, USA.
Patel S; Discovery Chemistry, Genentech, South San Francisco, California, USA.
Xu M; Translational Immunology, Genentech, South San Francisco, California, USA.
Maher J; Safety Assessment, Genentech, South San Francisco, California, USA.
McKenzie BS; Translational Immunology, Genentech, South San Francisco, California, USA.
Vucic D; Early Discovery Biochemistry, Genentech, South San Francisco, California, USA.
Źródło:: Journal of leukocyte biology [J Leukoc Biol] 2020 Jun; Vol. 107 (6), pp. 941-952. Date of Electronic Publication: 2020 Jan 27.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: 2023- : Oxford : Oxford University Press
Original Publication: New York : Alan R. Liss, c1984-
MeSH Terms:: Dermatitis/*genetics
Herpesviridae Infections/*genetics
Receptor-Interacting Protein Serine-Threonine Kinases/*genetics
Skin/*immunology
Vaccinia/*genetics
Animals ; Chronic Disease ; Dermatitis/immunology ; Dermatitis/pathology ; Dermatitis/virology ; Disease Models, Animal ; Gammaherpesvirinae/immunology ; Gammaherpesvirinae/pathogenicity ; Gene Expression Regulation ; Herpesviridae Infections/pathology ; Herpesviridae Infections/virology ; Inflammation ; Liver/immunology ; Liver/pathology ; Liver/virology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Kinase Inhibitors/pharmacology ; Protein Kinases/deficiency ; Protein Kinases/genetics ; Protein Kinases/immunology ; Receptor-Interacting Protein Serine-Threonine Kinases/antagonists & inhibitors ; Receptor-Interacting Protein Serine-Threonine Kinases/deficiency ; Receptor-Interacting Protein Serine-Threonine Kinases/immunology ; Signal Transduction ; Skin/pathology ; Skin/virology ; Testis/immunology ; Testis/pathology ; Testis/virology ; Vaccinia/immunology ; Vaccinia/pathology ; Vaccinia/virology ; Vaccinia virus/immunology ; Vaccinia virus/pathogenicity ; Virus Replication/immunology
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Contributed Indexing:: Keywords: MLKL; RIP1; RIP3; RIPK1; RIPK3; caspase
Substance Nomenclature:: 0 (Protein Kinase Inhibitors)
EC 2.7.- (MLKL protein, mouse)
EC 2.7.- (Protein Kinases)
EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
EC 2.7.11.1 (Ripk3 protein, mouse)
Entry Date(s):: Date Created: 20200128 Date Completed: 20201104 Latest Revision: 20201104
Update Code:: 20240104
PubMed Central ID:: PMC7317411
DOI:: 10.1002/JLB.3MA1219-398R
PMID:: 31985117
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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.
(© 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology.)

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