miR-369-3p modulates inducible nitric oxide synthase and is involved in regulation of chronic inflammatory response

Abstract

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.

Knockdown of long non‑coding RNA DLEU2 suppresses idiopathic pulmonary fibrosis by regulating the microRNA‑369‑3p/TRIM2 axis

“…Functionally, miR-369-3p overexpression inhibited the viability and motility of HCC cells ( 29 ). miR-369-3p expression was decreased in the inflamed intestinal regions obtained from patients with inflammatory bowel disease and the overexpression of miR-369-3p alleviated the inflammatory response in response to lipopolysaccharide ( 30 ). Consistent with the findings of previous studies, the expression levels of miR-369-3p were also decreased in TGF-β1-stimulated A549 cells and lung tissues from mice with BLM-induced fibrosis in the present study.…”

Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer

“…miRNA can regulate arginine metabolism by regulating the expression of key molecules in arginine metabolism pathway, such as ASS ( Bates et al, 2010 ; Tu et al, 2020 ), ARG1 ( Bates et al, 2010 ; Yoo et al, 2019 ), ARG2 ( Dunand-Sauthier et al, 2014 ; Jin et al, 2014 ; Kim et al, 2017 ; Wang Y. et al, 2017 ), CAT-1 ( Chang et al, 2004 ; Li Y. et al, 2018 ), ODC ( Jagannathan et al, 2015 ) and NOS ( Perske et al, 2010 ; Yan et al, 2011 ; Guo et al, 2012 ; Sun et al, 2012 ; Zhu et al, 2013 ; Li et al, 2014 , 2017 , Li H.T. et al, 2018 ; Fu et al, 2015 ; Jiang et al, 2015 ; Zhang et al, 2015 , 2020 ; Rasheed et al, 2016 ; Reilly et al, 2016 ; Muxel et al, 2017 , 2018 ; Wang C. et al, 2017 , Wang et al, 2019 ; Cui et al, 2020 ; Lin et al, 2020 ; Scalavino et al, 2020 ; Table 1 ). It has been found that multiple miRNAs could target the same enzyme or transporter protein, and the same molecule could also be regulated by multiple miRNAs.…”

microRNAs involved in psoriasis and cardiovascular diseases

“…In keeping, miR-369 overexpression in these cells significantly decreased cytokine production (i.e. TNFα, IL6, IL-12, IL-1α, IL-1β) in response to LPS, and some anti-inflammatory cytokines, such as IL-10 and IL-1RA, were indirectly increased (76).…”

“…miR-369 expression levels were found increased in serum samples and skin tissues deriving from psoriatic patients compared to healthy subjects and a positive correlation exists between skin miR-369 levels and PASI (64,75). miR-369 has emerged as a key regulator of inflammatory response in dendritic cells, since it decreases LPS-induced NO production, by targeting directly iNOS expression, and simultaneously inhibiting nuclear translocation of NF-kB (76). In keeping, miR-369 overexpression in these cells significantly decreased cytokine production (i.e.…”

“…miR-369 has emerged as a key regulator of inflammatory response in dendritic cells since it decreases LPS-induced NO production, by directly targeting iNOS expression and simultaneously inhibiting nuclear translocation of NFKB ( 76 ). In keeping with this, miR-369 overexpression in these cells significantly decreased cytokine production (i.e.…”