کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6002691 | 1182977 | 2013 | 8 صفحه PDF | دانلود رایگان |
The effect of bisoprolol on dendritic cell (DC) migration was investigated, including the analysis of protein expression, cytokine secretion and activation of the PI3K-pathway. The chemotactic cell numbers in cholesterol-loaded DCs treated with epinephrine were significantly decreased by 26.66 ± 6.29% (6 h), 35.67 ± 2.91% (12 h) and 29.33 ± 1.09% (24 h). This effect was significantly reversed by 46.00 ± 10.65% (6 h), 64.25 ± 6.77% (12 h) and 55.74 ± 5.51% (24 h) when bisoprolol and epinephrine were both present. In cholesterol-loaded DCs, treatment with epinephrine significantly increased AR-β1 protein expression by 56.99 ± 4.87%, but inhibited β-arrestin 2 and CCR7 protein expression by 30.51 ± 4.22% and 25.31 ± 0.04%, respectively. These effects were reversed by bisoprolol by 36.87 ± 4.40%, 41.47 ± 3.95% and 30.14 ± 0.54%, respectively. TNF-α and MMP9 levels were decreased by 68.33 ± 4.00% and 39.57 ± 9.21% in cholesterol-loaded DCs treated with epinephrine. In contrast, when bisoprolol and epinephrine were administered together, the secretion of these proteins was significantly increased by 233.81 ± 37.06 % and 76.66 ± 14.21%, respectively. Treatment with epinephrine decreased PI3K-phosphorylation by 31.88 ± 2.79%, 40.24 ± 5.69% and 30.93 ± 4.66% at 15, 30 and 60 min, respectively, whereas the effect of epinephrine on the expression of phosphorylated PI3K was reversed by 49.49 ± 12.12%, 70.93 ± 16.14% and 47.62 ± 6.00%, respectively, when cells were treated with both bisoprolol and epinephrine. Wortmannin inhibited the effects of bisoprolol on PI3K-phosphorylation (38.63 ± 6.12%), the expression of CCR7 (23.4 ± 2.72%), the secretion of TNF-α (69.46 ± 4.48%) and MMP9 (43.15 ± 4.63%), and the number of chemotactic cells (36.84 ± 5.22%). This is the first study to establish a signaling pathway, epinephrine-AR-β1-β-arrestin2-PI3K-MMP9/CCR7, which plays a critical role in the migration of DCs.
Journal: Thrombosis Research - Volume 131, Issue 3, March 2013, Pages 230-237