Zusammenfassung
Objective-Mouse aorta smooth muscle cells (SMC) express tumor necrosis factor receptor superfamily member 1A (TNFR-1) and lymphotoxin beta-receptor (LT beta R). Circumstantial evidence has linked the SMC LT beta R to tertiary lymphoid organogenesis in hyperlipidemic mice. Here, we explored TNFR-1 and LT beta R signaling in cultured SMC. Methods and Results-TNFR-1 signaling activated the classical ...
Zusammenfassung
Objective-Mouse aorta smooth muscle cells (SMC) express tumor necrosis factor receptor superfamily member 1A (TNFR-1) and lymphotoxin beta-receptor (LT beta R). Circumstantial evidence has linked the SMC LT beta R to tertiary lymphoid organogenesis in hyperlipidemic mice. Here, we explored TNFR-1 and LT beta R signaling in cultured SMC. Methods and Results-TNFR-1 signaling activated the classical RelA NF-kappa B pathway, whereas LT beta R signaling activated the classical RelA and alternative RelB NF-kappa B pathways, and both signaling pathways synergized to enhance p100 inhibitor processing to the p52 subunit of NF-kappa B. Microarrays showed that simultaneous TNFR-1/LT beta R activation resulted in elevated mRNA encoding leukocyte homeostatic chemokines CCL2, CCL5, CXCL1, and CX3CL1. Importantly, SMC acquired features of lymphoid tissue organizers, which control tertiary lymphoid organogenesis in autoimmune diseases through hyperinduction of CCL7, CCL9, CXCL13, CCL19, CXCL16, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. TNFR-1/LT beta R cross-talk resulted in augmented secretion of lymphorganogenic chemokine proteins. Supernatants of TNFR-1/LT beta R-activated SMC markedly supported migration of splenic T cells, B cells, and macrophages/dendritic cells. Experiments with ltbr(-/-) SMC indicated that LT beta R-RelB activation was obligatory to generate the lymphoid tissue organizer phenotype. Conclusion-SMC may participate in the formation of tertiary lymphoid tissue in atherosclerosis by upregulation of lymphorganogenic chemokines involved in T-lymphocyte, B-lymphocyte, and macrophage/dendritic cell attraction. (Arterioscler Thromb Vasc Biol. 2010;30:395-402.)
Altmetric