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Inflammasomes—New Contributors to Blood Diseases

Inflammasomes are intracellular multimeric complexes that cleave the precursors of the IL-1 family of cytokines and various proteins, found predominantly in cells of hematopoietic origin. They consist of pattern-recognition receptors, adaptor domains, and the enzymatic caspase-1 domain. Inflammasome...

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Autores principales: Tomasik, Jaromir, Basak, Grzegorz Władysław
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331764/
https://www.ncbi.nlm.nih.gov/pubmed/35897704
http://dx.doi.org/10.3390/ijms23158129
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author Tomasik, Jaromir
Basak, Grzegorz Władysław
author_facet Tomasik, Jaromir
Basak, Grzegorz Władysław
author_sort Tomasik, Jaromir
collection PubMed
description Inflammasomes are intracellular multimeric complexes that cleave the precursors of the IL-1 family of cytokines and various proteins, found predominantly in cells of hematopoietic origin. They consist of pattern-recognition receptors, adaptor domains, and the enzymatic caspase-1 domain. Inflammasomes become activated upon stimulation by various exogenous and endogenous agents, subsequently promoting and enhancing inflammatory responses. To date, their function has been associated with numerous pathologies. Most recently, many studies have focused on inflammasomes’ contribution to hematological diseases. Due to aberrant expression levels, NLRP3, NLRP1, and NLRC4 inflammasomes were indicated as predominantly involved. The NLRP3 inflammasome correlated with the pathogenesis of non-Hodgkin lymphomas, multiple myeloma, acute myeloid leukemia, lymphoid leukemias, myelodysplastic neoplasms, graft-versus-host-disease, and sickle cell anemia. The NLRP1 inflammasome was associated with myeloma and chronic myeloid leukemia, whereas NLRC4 was associated with hemophagocytic lymphohistiocytosis. Moreover, specific gene variants of the inflammasomes were linked to disease susceptibility. Despite the incomplete understanding of these correlations and the lack of definite conclusions regarding the therapeutic utility of inflammasome inhibitors, the available results provide a valuable basis for clinical applications and precede upcoming breakthroughs in the field of innovative treatments. This review summarizes the latest knowledge on inflammasomes in hematological diseases, indicates the potential limitations of the current research approaches, and presents future perspectives.
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spelling pubmed-93317642022-07-29 Inflammasomes—New Contributors to Blood Diseases Tomasik, Jaromir Basak, Grzegorz Władysław Int J Mol Sci Review Inflammasomes are intracellular multimeric complexes that cleave the precursors of the IL-1 family of cytokines and various proteins, found predominantly in cells of hematopoietic origin. They consist of pattern-recognition receptors, adaptor domains, and the enzymatic caspase-1 domain. Inflammasomes become activated upon stimulation by various exogenous and endogenous agents, subsequently promoting and enhancing inflammatory responses. To date, their function has been associated with numerous pathologies. Most recently, many studies have focused on inflammasomes’ contribution to hematological diseases. Due to aberrant expression levels, NLRP3, NLRP1, and NLRC4 inflammasomes were indicated as predominantly involved. The NLRP3 inflammasome correlated with the pathogenesis of non-Hodgkin lymphomas, multiple myeloma, acute myeloid leukemia, lymphoid leukemias, myelodysplastic neoplasms, graft-versus-host-disease, and sickle cell anemia. The NLRP1 inflammasome was associated with myeloma and chronic myeloid leukemia, whereas NLRC4 was associated with hemophagocytic lymphohistiocytosis. Moreover, specific gene variants of the inflammasomes were linked to disease susceptibility. Despite the incomplete understanding of these correlations and the lack of definite conclusions regarding the therapeutic utility of inflammasome inhibitors, the available results provide a valuable basis for clinical applications and precede upcoming breakthroughs in the field of innovative treatments. This review summarizes the latest knowledge on inflammasomes in hematological diseases, indicates the potential limitations of the current research approaches, and presents future perspectives. MDPI 2022-07-23 /pmc/articles/PMC9331764/ /pubmed/35897704 http://dx.doi.org/10.3390/ijms23158129 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Tomasik, Jaromir
Basak, Grzegorz Władysław
Inflammasomes—New Contributors to Blood Diseases
title Inflammasomes—New Contributors to Blood Diseases
title_full Inflammasomes—New Contributors to Blood Diseases
title_fullStr Inflammasomes—New Contributors to Blood Diseases
title_full_unstemmed Inflammasomes—New Contributors to Blood Diseases
title_short Inflammasomes—New Contributors to Blood Diseases
title_sort inflammasomes—new contributors to blood diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331764/
https://www.ncbi.nlm.nih.gov/pubmed/35897704
http://dx.doi.org/10.3390/ijms23158129
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