The Dynamic Expression Of AIF-1and Effects Of Purified AIF-1Intervention On Mice Infected With Schistosoma Japonicum

Allograft inflammatory factor-1(AIF-1), originally cloned by Utans from rat andhuman heart allograft under chronic rejection, is expressed in various inflammatoryconditions. Subsequent studies found AIF-1has a highly conserved sequence amongdifferent species and is found in invertebrates and vertebrates including marine sponges,fish, mouse, rat, pig, and human. This polypeptide has complex and comprehensivefunctions and plays important roles in diversiform immune response.AIF-1is an early inflammatory factor and up-regulated in autoimmune diseases,transplanted organs and experimental autoimmune lesions. When AIF-1transgenic mice(Tgm) administrated with2,4,6-trinitrobenzene sulphonic acid(TNBS), the induced colitiswas ameliorated compared with that non-transgenic littermates, and Morohashi consideredAIF-1regulated Th1-type inflammatory response by down-regulating IL-1β in the colon.Mishima found over-expression of AIF-1caused the immune response biasing from Th1toTh2type. These reported studies show AIF-1takes vital roles by linkage with macrophages,lymphocytes, endothelial cells and some cytokines such as TNF-α, IFN-γ and TGF-β andregulating the immune system. Schistosomiasis is an epidemic disease, and its immunopathological reactions againstschistosome eggs trapped in the liver lead to hepatosplenic inflammation and liver fibrosis,which threaten people’s health and interfere with the economic development. We speculatedthat AIF-1was over-expressed in tissues of the infected host’s liver and spleen similar withother immune inflammatory diseases, and if we intervene in the infected mice with thepurified AIF-1, the polypeptide can affect the course of the disease. So we designed,executed this experiment and verified our preliminary conjecture. The experiment consistsof two parts.The first part: Our data firstly verified that the liver of BALB/c mice infected with S.japonicum over-expressed AIF-1, and the level of AIF-1peaked at the early stage ofinfection, and then declined gradually, which were in accordance with the fluctuation of thesera ALT. So AIF-1may be an early and sensitive biomarker reflecting the hepatocytesinjury. To examine the secretion of AIF-1in vitro by splenocytes, the unfractionated spleniccells were incubated with SEA for72h. It is intriguing that the concentration of AIF-1in thecultures was lower in the infected mice than the controls. The naive splenocytes of controlmice can synthesize and secrete AIF-1directly when stimulated with SEA for72h,indicating AIF-1is an early inflammatory factor. We tested the expression of AIF-1, TNF-αand TGF-β and found these cytokines had some correlation about quantitative changing.These data demonstrate that AIF-1may play important roles in the development of hepaticschistosomiasis via affecting and acting with other cytokines.The second part: We intervened in the infected mice with purified AIF-1andconstituted the control groups. We discovered the hepatocytes injury in the intervened micewere severer than that in the controls at5weeks post-infection, but the mice were ameliorative in necrosis and fibrosis at the chronic stage of infection. Using Western blot,RT-PCR and ELISA, we found the expression of AIF-1was strengthened gradually with thelength of infection in the tissues of AIF-1intervened mice. The results demonstrate that theintervention of AIF-1increase the effective concentration of AIF-1at the chronic stage ofinfection and the AIF-1can protect the liver. That’s to say, the purified AIF-1may preventand treat the chronic hepatic schistosomiasis effectively.Intensively studying the molecular mechanism of anti-fibrosis of AIF-1in theschistosomiasis is beneficial to prevent and treat other fibrotic lesions, such as systemsclerosis and rheumatoid arthritis, in that these diseases have the similar pro-fibroticcellular and molecular principle. How to select the more effective intervention time anddose is also the next task for us.In summary, our data first demonstrate:1. AIF-1was over-expressed in the liver tissues of BALB/c mice infected with S.japonicum, and the level peaked at the early-stage of infection, and thendeclined gradually.2. AIF-1is an early inflammatory factor and play vital roles in the pathogenesisof schistosomiasis in linkage with TNF-α and TGF-β.3. The intervention of AIF-1increased the effective concentration of AIF-1in theintervened mice at the chronic stage of infection, and the liver necrosis andfibrosis were alleviated conversely.4. The purified AIF-1can prevent and treat the chronic hepatic schistosomiasiseffectively.