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Suppression of lncRNA NLRP3 inhibits NLRP3-triggered inflammatory responses in early acute lung injury
- Source :
- Cell Death and Disease, Vol 12, Iss 10, Pp 1-15 (2021), Cell Death & Disease
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- Acute lung injury (ALI) is a common lung pathology that is accompanied by alveolar macrophage (AM) activation and inflammatory response. This study investigated the role of the long non-coding RNA NONRATT004344 (hereafter named lncRNA NLRP3) in regulating the Nod-like receptor protein 3 (NLRP3)-triggered inflammatory response in early ALI and the underlying mechanism as well. We established LPS-induced ALI models to explore their interactive mechanisms in vitro and in vivo. Luciferase reporter assays were performed to determine that miR-138-5p could bind to lncRNA NLRP3 and NLRP3. We observed increased lncRNA NLRP3 expression, decreased miR-138-5p expression, NLRP3 inflammasome activation, and upregulated caspase-1, IL-1β, and IL-18 expression in the LPS-induced ALI model. Furthermore, lncRNA NLRP3 overexpression activated the NLRP3 inflammasome and promoted IL-1β and IL-18 secretion; the miR-138-5p mimic abolished these effects in vivo and in vitro. Consistently, miR-138-5p inhibition reversed the effects of lncRNA NLRP3 silencing on the expression of NLRP3-related molecules and inhibition of the NLRP3/caspase-1/IL-1β signalling pathway. Mechanistically, lncRNA NLRP3 sponging miR-138-5p facilitated NLRP3 activation through a competitive endogenous RNA (ceRNA) mechanism. In summary, our results suggested that lncRNA NLRP3 binding miR-138-5p promotes NLRP3-triggered inflammatory response via lncRNA NLRP3/miR-138-5p/NLRP3 ceRNA network (ceRNET) and provides insights into the treatment of early ALI.
- Subjects :
- Lipopolysaccharides
Male
Cancer Research
Transcription, Genetic
Inflammasomes
Acute Lung Injury
Interleukin-1beta
Immunology
Lung injury
Models, Biological
Article
Cell Line
Inflammasome
Rats, Sprague-Dawley
Cellular and Molecular Neuroscience
Downregulation and upregulation
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Gene silencing
RNA, Messenger
Receptor
3' Untranslated Regions
Lung
Inflammation
Base Sequence
integumentary system
QH573-671
Competing endogenous RNA
Chemistry
Caspase 1
Interleukin-18
Cell Biology
Hedgehog signaling pathway
Up-Regulation
MicroRNAs
Cancer research
Alveolar macrophage
RNA, Long Noncoding
Bacterial infection
Cytology
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....bc90366c319179dafa5e4cbbc69633be