Dysregulation of Inflammasome Priming and Activation by MicroRNAs in Human Immune-Mediated Diseases.
Nina BoxbergerMichael HeckerUwe K ZettlPublished in: Journal of immunology (Baltimore, Md. : 1950) (2019)
Inflammasomes are protein complexes that respond to a wide range of pathogens and cellular damage signals. Their activation prompts the caspase-1-mediated cleavage of the proinflammatory cytokines IL-1β and IL-18. Inflammasome dysregulation has been demonstrated to play a role in a range of diseases involving the adaptive immune system like multiple sclerosis, rheumatic diseases, and type 1 diabetes. Priming and activation of inflammasomes can be modulated by microRNAs (miRNAs), small noncoding RNAs that regulate gene expression posttranscriptionally. miRNAs, such as miR-223-3p, have been demonstrated to directly target the inflammasome components NLRP3, caspase-1, and caspase-8. Other miRNAs like miR-155-5p modulate TLR-, IL-1R-, TNFR-, and IFNAR-mediated signaling pathways upstream of the inflammasomes. In this study, we discuss how a more detailed elucidation of miRNA-driven inflammasome regulation helps in understanding the molecular processes underlying immune-mediated human diseases, holds potential for the identification of biomarkers and may offer novel targets for the development of future therapeutics.
Keyphrases
- gene expression
- endothelial cells
- multiple sclerosis
- cell death
- type diabetes
- induced apoptosis
- signaling pathway
- pluripotent stem cells
- dna methylation
- oxidative stress
- small molecule
- immune response
- endoplasmic reticulum stress
- current status
- white matter
- risk assessment
- adipose tissue
- climate change
- protein protein
- gram negative
- bioinformatics analysis