miR-369-3p modulates inducible nitric oxide synthase and is involved in regulation of chronic inflammatory response.
Viviana ScalavinoMarina LisoElisabetta CavalcantiIsabella GiganteAntonio LippolisMauro MastronardiMarcello ChieppaGrazia SerinoPublished in: Scientific reports (2020)
Dendritic cells are the most important antigen-presenting cells that link the innate and acquired immune system. In our previous study, we identified that the upregulation of miR-369-3p suppresses the LPS-induced inflammatory response, reducing C/EBP-β, TNFα and IL-6 production. With the aim of gaining further insight into the biological function of miR-369-3p during acute inflammatory response, in the present study we identified novel gene targets of miR-369-3p and demonstrated the suppressive ability of these genes on the inflammatory dendritic cells. Bioinformatic analyses revealed that iNOS is a potential target of miR-369-3p. We demonstrated that the ectopic induction of miR-369-3p markedly reduced iNOS mRNA and protein as well as NO production. Moreover, we found that the upregulation of miR-369-3p decreased the release of TNFα, IL-6, IL-12, IL-1α, IL-1β in response to LPS, and increased the production of anti-inflammatory cytokines such as IL-10 and IL-1RA. In addition, LPS-induced nuclear translocation of NF-kB was inhibited by miR-369-3p. Levels of miR-369-3p were decreased in human inflamed regions of human intestine obtained from IBD patients. Our results provide novel additional information on miR-369-3p as a potential core of the signaling regulating the inflammatory response. These findings suggest that miR-369-3p should be considered as a potential target for the future development of new molecular therapeutic approaches.
Keyphrases
- inflammatory response
- lps induced
- lipopolysaccharide induced
- dendritic cells
- toll like receptor
- nitric oxide synthase
- immune response
- endothelial cells
- rheumatoid arthritis
- signaling pathway
- induced apoptosis
- nitric oxide
- cell proliferation
- ejection fraction
- healthcare
- poor prognosis
- intensive care unit
- drug induced
- binding protein
- risk assessment
- human health
- gene expression
- liver failure
- genome wide identification
- climate change
- copy number
- prognostic factors
- patient reported outcomes
- mechanical ventilation
- extracorporeal membrane oxygenation
- cell death
- acute respiratory distress syndrome
- health information
- ankylosing spondylitis
- respiratory failure
- small molecule
- disease activity
- interstitial lung disease
- ulcerative colitis