TIM-3 is involved in NO imbalance of Atherosclerosis through the IkappaB/NF-kappaB Pathway (91.6)

Abstract TIM-3 (T cell immunoglobulin and mucin domain-3) is proved to regulate the immune system in many inflammaroty diseases. However, the role of TIM-3 on atherosclerosis has not been studied. We found TIM-3 was highly expressed on monocytes/macrophages of human peripheral blood,but low on T cells, either CD4+ or CD8+ T cells. And the level of Tim-3 expression on monocytes/macropahges from patients with atherosclerotic disease was higher than that from healthy subjects (93.35¡À12.14% vs 81.04¡À 24.07%,t=4.968,P<0.0001). Immunochemistry staining demonstrated the upregualtion of Tim-3 on RAW264.7, a macrophage like cell line, incubated with oxidized low-density lipoprotein (oxLDL) or LPS. Moreover, Tim-3 blocking antibody acted as an adjuvant during Nitic oxide (NO) production of RAW 264.7.Consistent to that,overexpresstion of Tim-3 by transfection inhibited NO production of RAW264.7.Futher study showed Tim-3 blocking antibody enhanced phosphorylation of NF-kappaB p65 and degradation of IkappaB.Thus TIM-3 inhibits NO production of macrophages mainly through the IkappaB/NF-kappaB pathway and is involved in NO imbalance in Atherosclerosis. correspondence to: Professor Chunhong Ma, Institute of Immunology, Shandong University School of Medicine.E-mail address: machunhong@sdu.edu.cn.