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Inflammasome activation by cell volume regulation and inflammation-associated hyponatremia: A vicious cycle

Authors
 J.H. Kim  ;  J.H. Park  ;  M. Eisenhut  ;  J.W. Yu  ;  J.I. Shin 
Citation
 MEDICAL HYPOTHESES, Vol.93 : 117-121, 2016 
Journal Title
MEDICAL HYPOTHESES
ISSN
 0306-9877 
Issue Date
2016
MeSH
Animals ; Cell Size* ; Cells, Cultured ; Central Nervous System/metabolism ; Humans ; Hyponatremia/metabolism ; Hyponatremia/physiopathology* ; Inappropriate ADH Syndrome/metabolism ; Inappropriate ADH Syndrome/physiopathology ; Inflammasomes/metabolism* ; Inflammation ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Lysosomes/metabolism ; Mice ; Models, Theoretical ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Neurons/pathology ; Osmolar Concentration ; Osmosis ; Rats ; Rats, Wistar ; Stress, Mechanical
Abstract
Inflammasomes are caspase-1-activating molecular platforms that produce active interleukin (IL)-1β and are implicated in various central nervous system (CNS) diseases. These multi-protein complexes can be activated by exposure of cells to low osmolality. The inflammasome nucleotide-binding and oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) is hereby the main sensor of cellular osmolality. IL-1β was found to stimulate the secretion of antidiuretic hormone (ADH) from the posterior pituitary gland either by action of prostaglandins or indirectly by causing the release of IL-6. Based on these findings, we hypothesize that the hyponatremia caused by a wide range of CNS diseases is able to induce significant cell swelling with induction of a hyposmotic intracellular environment, which activates the NLRP3 inflammasome, causing the release of IL-1β and induced by IL-1β, IL-6, which increases the production of ADH that leads to more profound hyponatremia. Supportive evidence for this hypothesis is the finding that IL-1 injection can induce ADH release and hyposmotic effect of ADH induced hyponatremia can, via the mechanical effect of cell swelling, activate transient receptor potential channels, which via transforming growth factor β-activated kinase 1 activate NLRP3. Implications of this hypothesis, if confirmed, would include that hyponatremia can be exacerbated through this vicious cycle but also that the inflammasomes are key mediators of this process. Confirmation of this hypothesis would have implications for prevention and clinical management of changes in patients sodium levels related to syndrome of inappropriate antidiuretic hormone secretion (SIADH) with interventions targeting inflammatory mediator production and function of inflammasomes with the potential of prevention of permanent brain damage in a wide range of CNS diseases.
Full Text
http://www.sciencedirect.com/science/article/pii/S0306987716301414?via%3Dihub
DOI
10.1016/j.mehy.2016.05.018
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jae Il(신재일) ORCID logo https://orcid.org/0000-0003-2326-1820
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151990
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