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.
Highlights
Dendritic cells are the most important antigen-presenting cells that link the innate and acquired immune system
We demonstrated that miR-369-3p, regulating C/EBP-β, TNFα and IL-6, is responsible for the anti-inflammatory effect of quercetin in bone marrow-derived dendritic cells (BMDCs)
This miRNA was highly upregulated after LPS stimulation. miR-155, by targeting SOCS1 and SHIP1, was a positive regulator of the production of several pro-inflammatory cytokines including IL-6, IL-23, IL-12, and TNFα18
Summary
Dendritic cells are the most important antigen-presenting cells that link the innate and acquired immune system. We identified that the upregulation of miR-369-3p suppresses the LPS-induced inflammatory response, reducing C/EBP-β, TNFα and IL-6 production. The recognition of pathogen-associated molecules by antigen-presenting cells is crucial step to the initiation of the immune response[2] resulting in DC maturation, characterized by the expression of numerous cell surface molecules. These include increased major histocompatibility complex class II (MHC II) and co-stimulatory molecules (CD80, CD86 and CD40) and the production of soluble factors like cytokines and chemokines[3]. Quercetin exposure, we confirm the protective role of miR-369-3p in DCs stimulated by LPS in suppressing the LPS-induced inflammatory r esponse[11]
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