Shear Stress Modulates Resistin‐Induced CC Chemokine Ligand 19 Expression in Human Aortic Endothelial Cells

Abstract

Resistin may be an important link between obesity and diabetes. Recent studies have suggested an association between resistin and atherogenic processes. In addition, CCL19 is highly expressed in human atherosclerotic lesions. The interplays among resistin, CCL19, and shear stress in regulating vascular endothelial function are not clearly understood. In the present study, resistin stimulation induced dose- and time-dependent CCL19 expression in human aortic endothelial cells (HAECs). By using neutralizing antibody and small interfering (si)RNA, we demonstrated that toll-like receptor 4 (TLR4) is critical for resistin-induced CCL19 expression. Transcription factor ELISA and chromatin immunoprecipitation assays showed that resistin increased NF-κB-DNA binding activities in ECs. Inhibition of NF-κB activation by specific siRNA blocked the resistin-induced CCL19 promoter activity and expression. Preshearing of ECs for 12 h at 20 dyn/cm(2) inhibited the resistin-induced NF-κB activation and CCL19 expression. Our findings serve to elucidate the molecular mechanisms underlying the resistin induction of CCL19 expression in ECs and the shear-stress protection against this induction.

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

“…TLR-4 is recognized to have a key function in the host defence against Gram-negative bacteria, viruses, fungi and mycoplasma [10], but also in the patho-physiology of several age-related diseases [9,11], including CVDs, as stressed in our studies [4,8,11,12] and described by other groups [13][14][15]. Recently, its role has emerged in maintaining aortic homeostasis, but also in establishing aorta aneurysm [4,8,[16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

“…In fact, the role of TLR-4 mediated receptor signaling pathway in the context of aorta diseases is also emerging [16][17][18][19][20][21][22][23][24][25][26][27][28][29]. In particular, our group postulates its fundamental contribution to the development of sporadic TAA, as reported in the above mentioned model [4,8].…”

Resistin promotes CCL4 expression through toll-like receptor-4 and activation of the p38-MAPK and NF-κB signaling pathways: implications for intervertebral disc degeneration

“…p38-MAPK pathway is critical for resistin-induced SDF-1 expression mediated by TLR4 in gastric cancer cells 23 . Additionally, HR Yu et al demonstrated that TLR4 is critical for resistin-induced CCL19 expression using a neutralizing antibody and siRNA in human aortic endothelial cells 24 . Our data showed that pharmacological inhibitors of TLR4 and TLR4 siRNA application could inhibit resistin-induced CCL4 expression, which was further confirmed with co-immunoprecipitation.…”

The prognostic value and molecular properties of tertiary lymphoid structures in oesophageal squamous cell carcinoma

“…Therefore, the decreased expression of CCL19 in the B cell zones of mature TLSs was probably due to the decreased percentages of other CCL19‐secreting cells, such as fibroblasts 22 and endothelial cells. 23 T cells in the B cell zones of immature TLSs were with higher expression of naïve T cell marker SELL (Table S9 ) and an increased T naïve signature (Figure 4C ; Table S10 ). Antigens are presented by FDCs to B cells and by B cells and DCs to T cells in the B cell zones of TLSs.…”