Natural Small Molecule Kae Inhibits VSV Infection And LPS-induced Inflammatory Response

Innate immunity is regarded as the first defender in corporal anti-infection immunity.When pathogens invade organism,it can be recognized by the pattern recognition receptors(PRRs)specifically and initiate anti-infectious immune response through activating downstream signaling pathways.Type ? interferon and pro-inflammatory cytokines,produced under the regulation of RIG and NF-?B signaling pathways,can induce a series of immune response and thus play an important role in infection immunity.TLR and RLR are two important pattern recognition receptors.RLR can recognize RNA virus such as VSV to activate RIG-? signaling pathway and promote type ?interferon production and secretion.In LPS-induced anti-infection immunity,TLR4 can discern LPS so that to activate downstream NF-?B and(or)MAPK signal pathway,prompting the phosphorylation of P65 enter into nuclear,inducing production and secretion of pro-inflammatory cytokines such as IL-1?,IL-6 and TNF-?.Natural drug is one of the most important drugs in the treatment of infectious diseases.In recent years,finding good curative effect and no side effects of natural drug treatment of infectious diseases from the natural plant are become a research hotspot.Flavonoids drugs as a category of natural medicines,have a variety of functions and role.We found the natural small molecule kaempferol 7,4'-dimethyl ether 3-O-?-D-glucopyranoside(hereinafter referred to as the Kae)could increase the production of VSV-induced type ? interferon,at the same time suppress the pro-inflammatory cytokines induced by LPS.RIG-I signaling pathway has several important molecular nodes,including RIG-I,MAVS,TBK1 and IRF3.We found that Kae could promotes TBK1 phosphorylation of VSV-induced to promote production of type ? interferon in mouse primary peritoneal macrophages.Meanwhile,Kae could inhibit LPS-induced IKK?/? and I?B? phosphorylation to inhibit production of pro-inflammatory cytokine.In conclusion,we validated that Kae could regulate the generation of type ?interferon and pro-inflammatory cytokines by regulating the phosphorylation of TBK1,IKK?/? and I?B?.Type ? interferon and pro-inflammatory cytokines play an important role in anti-infectious immune response,and Kae plays a regulatory role in it.It is worth mentioning that Kae plays a role in both anti-virus and anti-inflammation upon the stimulation of VSV and LPS.This finding provides us a new visual angle to design new drugs that can resist virus and inhibit inflammation at the same time.