LRR-protein RNH1 dampens the inflammasome activation and is associated with COVID-19 severity.
Details
Serval ID
serval:BIB_4E57CCCF79FA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
LRR-protein RNH1 dampens the inflammasome activation and is associated with COVID-19 severity.
Journal
Life science alliance
ISSN
2575-1077 (Electronic)
ISSN-L
2575-1077
Publication state
Published
Issued date
06/2022
Peer-reviewed
Oui
Volume
5
Number
6
Pages
e202101226
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
Inflammasomes are cytosolic innate immune sensors of pathogen infection and cellular damage that induce caspase-1-mediated inflammation upon activation. Although inflammation is protective, uncontrolled excessive inflammation can cause inflammatory diseases and can be detrimental, such as in coronavirus disease (COVID-19). However, the underlying mechanisms that control inflammasome activation are incompletely understood. Here we report that the leucine-rich repeat (LRR) protein ribonuclease inhibitor (RNH1), which shares homology with LRRs of NLRP (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing) proteins, attenuates inflammasome activation. Deletion of RNH1 in macrophages increases interleukin (IL)-1β production and caspase-1 activation in response to inflammasome stimulation. Mechanistically, RNH1 decreases pro-IL-1β expression and induces proteasome-mediated caspase-1 degradation. Corroborating this, mouse models of monosodium urate (MSU)-induced peritonitis and lipopolysaccharide (LPS)-induced endotoxemia, which are dependent on caspase-1, respectively, show increased neutrophil infiltration and lethality in Rnh1 <sup>-/-</sup> mice compared with wild-type mice. Furthermore, RNH1 protein levels were negatively related with disease severity and inflammation in hospitalized COVID-19 patients. We propose that RNH1 is a new inflammasome regulator with relevance to COVID-19 severity.
Keywords
Animals, COVID-19/immunology, COVID-19/pathology, Carrier Proteins/metabolism, Caspase 1/metabolism, Humans, Inflammasomes/metabolism, Leucine-Rich Repeat Proteins/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B/metabolism, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism, Patient Acuity, Proteasome Endopeptidase Complex/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
14/03/2022 8:34
Last modification date
21/11/2022 8:18