The Mechanisms of Thymic Stromal Lymphopoietin in Atherosclerosis in ApoE-/-Mice
|School||Huazhong University of Science and Technology|
|Course||Department of Cardiology|
|Keywords||atherosclerosis TSLP immune tolerance|
Objective:There are lots of studys proved that atherosclerosis is a chronic disease including inflammatory and immune mechanisms. During its occurrence and development process, both immune cells and cytokines contribute to the atherosclerosis. In addition, inflammatory mediators also play a key role in the formation of plague. As a novel cytokine, whether TSLP can regulate the development of atherosclerosis through immuninflamatory response. Our study will discover the potential mechanisms by the establishment of atherosclerotic animal model.Methods and Results:Male ApoE-/-mice were injected subcutaneously in the nucchal area with recombinant mouse TSLP (600ng·250μl-1· mouse-1· day-1) or PBS for6consecutive days. Six days after treatment of TSLP, a Western-type diet was administered for10weeks. Then blood were acquired through inner canthus vein and mice were sacrificed by cervical dislocation.The area of atherosclerotic plague was evaluated by using oil red and HE staining. We use flow cytometry to assess the change of CD4+LAP+Tregs, CD4+CD25+Foxp3+Tregs, Th1, Th2, and Th17after TSLP injection in spleen. ELISA and Real-Time RT-PCR are used to detect the secretion of IFN-γ、IL-4、IL-12、IL-10、IL-17and TGF-β by spleen, serum and aortic plague. Then we found that mice treated with TSLP developed a substantially smaller atherosclerotic lesion size in the aortic sinus compared with PBS-treated control mice (3.20±0.48versus4.75±0.85×105μm2, p<0.01). Simultaneously, we found TSLP treatment reduced the percentage of plaque area that stained positive MAMO-2macrophages (28.25±9.72versus53.13±12.29%, p<0.05) and also a3-fold increase in Foxp3+Treg cells infiltration. Furthermore, we performed a-SMA and collagen staining of the plaques and found no statistical significance in staining between TSLP-treated mice and PBS-treated mice.Conclusion:With subcutaneous injection of TSLP, the area of plagues had an obvious decrease and the progession of atherosclerosis was inhibited. The potential mechanisms are maybe the regulation of immuninflamatory, induction of Tregs and secretion of related cytokines.