To Investigate The Mechanism Of Long Non-coding RNA CXORF36-AS In Regulating GM-CSF Expression

The innate immunity is the process by which the organism recognizes itself and exclude intruders.The innate immune system plays an important role as the first line of defense against invading microbes by sensing pathogen-associated molecular patterns(PAMPs)or danger-associated molecular patterns(DAMPs).The initiation of innate immune system is regulated by a variety of pattern recognition receptors(PRRs),including Toll-like receptors(TLR),RIG-I-like receptors(RLR)and so on,which enable the body to monitor extracellular activities and intracellular infections in order to maintain homeostasis.Upon pathogen invasion,these PRRs trigger the activation of NF-?B,type I interferon(IFN),or other inflammasome signaling pathways,which,in turn,leads to the production of a variety of proinflammatory and antiviral cytokines and chemokines,subsequently inducing adaptive immune responses.In recent years,the important role of long non-coding RNA(lncRNA)in innate immune regulation has been recognized.However,in fact,the regulatory role of lncRNA in innate immune response is still unclear and needs further study.Lipopolysaccharide(LPS)is the main component of the cell wall of gram negative bacteria.Toll-like receptor 4(TLR4),as a receptor stimulated by LPS,can trigger the innate immunity of the body.The purpose of this study is to investigate the transcriptional regulation mechanism of lncRNA-CXORF36-AS,which is dependent on TLR4/NF-kappa B signaling pathway,and its role in innate immunity.The research results are summarized as follows:(1)lncRNA-CXORF36-AS,which is dependent on TLR4/NF-kappa B signaling pathway,was screened by using LPS as an external stimulant to act on human macrophages U937 and intestinal epithelial cells SW480.(2)Study found that the expression of lncRNA-CXORF36-AS depended on TLR1/2/4 receptor,but not TLR3 receptor.(3)LncRNA-CXORF36-AS is an early response factor in innate immune response.(4)The expression of lncRNA-CXORF36-AS was significantly inhibited after treatment with inhibitors of NF-kappa B and MAPK signaling pathways,suggesting that the expression of lncRNA-CXORF36-AS depends on both NF-kappa B and MAPK signaling pathways.(5)LncRNA-CXORF36-AS can regulate the expression of GM-CSF.(6)The mechanism of lncRNA-CXORF36 regulating GM-CSF expression was further discussed.The results showed that lncRNA-CXORF36-AS could regulate the expression of GM-CSF at the transcriptional level by binding P65.In conclusion,we screened an lncRNA-CXORF36-AS dependent on TLR1/2/4 receptor,and CXORF36-AS can regulate GM-CSF expression at the transcriptional level through P65 interaction.