The Effect Of Prion Protein In LPS-induced Colitis

The cellular prion protein(PrP~c)is a kind of glycoprotein and sited on the surface of cell member by a GPI anchor.It's widely expressed in the various tissues and organs of vertebrates.Previous studies reported PrP~c might participate in immune regulation,signal transduction,cell adhesion and migration.However,the physiologic functions of PrP~c remain poorly understood.In this study,we induced inflammation by intraperitoneal injection of lipopolysaccharide(LPS)in three types of mice with different PrP~c expression level,named wide-type mice(WT),prion protein knock-out mice(KO)and prion protein-overexpressing mice(Tg20).The role of PrP~c in colitis was investigated by comparing the different inflammatory response among different genotypes.In this study,two experimental protocols were designed to induce colitis.Protocol1:mice were intraperitoneally injected one single high dose LPS(10 mg/kg)and observed for 6 days.Protocol 2:mice were repeatedly injected low dose LPS(1 mg/kg/d)for 6 days.The results show that in both Protocol 1 and Protocol 2,KO mice exhibited more serious diarrhea than WT and Tg20 mice(P<0.01).Immunohistochemistry data revealed that,in both Protocol 1 and Protocol 2,the colon tissues of KO mice had more CD4 positive cells than those of WT and Tg20 mice after 6 days of the first injection of LPS(P<0.05).In addition,the expression levels of pro-inflammatory cytokines in the colon tissues of KO mice were generally higher than those of WT mice after 6 days of the first injection of LPS in both 2 protocols.Importantly,the expression levels of CCL2,TNF?and IL-1?in the colon tissue of Tg20 mice were significantly lower than those of KO mice(P<0.05).In summary,these results showed that PrP~c deletion could aggravate the inflammatory response induced by LPS in the colon,with longer response time and delayed recovery.In contrary,overexpression of PrP~c could reduce the inflammation caused by LPS.