Study On The Alternation Of IRE1Pathway Gene Expressions And Cytokines In Intestine Of The Mouse Infected With The Parasite Trichina Spiralis

Endoplasmic reticulum stress(ERS) is caused when the physiological functions of ER aredisrupted by various stimuli, such as hypoxia, drug toxicity and infection etc. ERS exhibits thechanges in intraluminal calcium, altered oxidation environment and accumulation of unfolded ormisfolded protein in ER cavity. ERS protects the cells against damage in early reaction tovarious stimuli. However, the too severe sustained stimulation results in cell death. Theaccumulation of unfolded or misfolded protein in endoplasmic reticulum results in the unfoldedprotein response(UPR). PERK, IRE1, ATF6are three important members of ERS signalingpathways. The alteration of these molecules involved in the UPR indicate the occurrence of ERS.They play important roles to accumulate unfolded or misfolded protein in endoplasmicreticulum lumen.Trichinella spriralis is the most widespread zoonotic parasite in the world which affects thehealth of human and animals. It is unclear whether Trichinella spriralis causes ERS reaction inthe intestine of infected mice. In this study, the mice were inoculated with Trichinella spriralisand the expression of GRP78、IRE1and XBP1genes involved in IRE1signal pathway of ERSwere analyzed by the Real-time PCR and Western blot, and using ELISA to detect the intestinalinflammation. At day7post infection (PI), mRNA transcription levels of GRP78、IRE1andXBP1in jejunum were significantly increased (p<0.05); at day14PI, the mRNA molecules ofthese genes in IRE1signal pathway reached peak, especially, mRNA expression of GRP78significantly up-regulated (p<0.01); at day28PI, the level of expression of GRP78、IRE-1andXBP1dropped significantly and closed to the expression level of day7. Western blot confirmedthe production of GRP78protein in jejunum is accordance to the expression of its mRNAexpression. The GRP78protein expression at day14was markedly elevated comparing thelevel at day7and28post infection. In the duodenum, the mRNA expression of GRP78、IRE-1and XBP1were no significant difference comparing the control group (p>0.05). Thespontaneous secreted cytokines IL-10and TNF-a in duodenum and jejunum tissue fragmentcultures were significant increased while IL-12and IL-17were decreased at day7and day14PI.All these cytokines showed a recovery trend at day28PI. The results showed that GRP78、IRE1and XBP1genes and protein which involved in the UPR significantly changed in the jejunumtissue, and their up-regulate or down regrulate were accordance to the progress of intestinal inflammation and recovery in the mice infected with Trichinella spriralis. The results suggestthat endoplasmic reticulum stress may be involved in the pathogenesis of Trichinella spriralisintestinal infection. It may help for further exploring the relationship between parasitic diseaseand the endoplasmic reticulum stress reaction and better understanding the pathogenesis ofintestinal dysfunction during Trichinella priralis infection.