The Study Of The Effect Of IRAKs On Toll-like Receptor 4 Mediated Acute Anterior Uveitis And The Anti-inflammatory Mechanism Of Hedysarum Polybotrys Saccharide

Purpose:To investigate the protective effect of LPS preconditioning against EIU in rats.Methods:EIU in Wistar rats was developed by subcutaneous injection of LPS(200 μg).Lower dose of LPS(0.1 mg/kg,intraperitoneally)or its carrier was injected daily for five days before EIU induction.24 hours after EIU,eyes were examined then enucleated.The degree of inflammatory reaction was determined by routine histological examinations.Real-time RT-PCR and Western blot were used to determine the activation of NF-k B and expression of IRAK-1,IRAK-4 and IRAK-MResults:Repeated pre-administration of LPS induced a significant reduction of ocular inflammation,and the expression of NF-κb p65 in neurons.IRAK-1 and IRAK-4 expression was suppressed in endotoxin tolerance group,whereas IRAK-M was increased.Conclusions : Endotoxin tolerance has a protective effect against EIU,and upregulation of IRAK-M through TLR-signaling pathway is one of the most likely candidates to be involved in the observed phenomenon.Objective: To investigate the key genes and the inflammatory signaling pathway involved in the anti-inflammatory effect of HPS on rat model of EIU.Methods: EIU in Wistar rats was developed by subcutaneous injection of LPS(200 μg).HPS(400mg/kg,intraperitoneally)or its carrier was injected 24 h and 1h before EIU induction.24 hours after EIU,eyes were examined then enucleated.Total RNA was extract from iris-ciliary body.Gene expression microarrays were used to identify the differentially expressed genes(DEGs),and the DEGs were analyzed by a range of bioinformatics-based techniques including Gene Ontology(GO),Pathway analysis,and Gene Correlation Network.Results: The gene expression microarrays identified 322 DEGs,including 254 m RNA genes and 68 lnc RNA genes.The GO analysis reflected many important functions,and the pathway analysis also highlighted several signaling pathways.16 m RNA and 7 lnc RNA DEGs that were shown to play critical roles in the Gene Correlation Network.Conclusions: A primarily combined m RNA and lnc RNA gene expression analysis of HPS targets on EIU displayed a series of candidate genes,which indicated that the antiinflammatory effect of HPS relied on combined signal transduction pathways in vivo.