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Serum Levels of IL-1 β , IL-6, TGF- β , and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting.

Zhang R, Jiang F, Chen CS, Wang T, Feng J, Tao T, Qin X - Mediators Inflamm. (2015)

Bottom Line: Telmisartan could reduce inflammation.In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months.MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

ABSTRACT
Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS). Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs) that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor) attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

No MeSH data available.


Related in: MedlinePlus

Telmisartan suppresses MMP-9 expression by inhibiting Elk-1 phosphorylation in THP-1 cells induced by scratch-injured human umbilical vein endothelial cells (HUVECs) supernatants. (a) Growth inhibiting effects of telmisartan on THP-1 cells. THP-1 cells were treated with 1.25, 2.5, 5, 10, 20, and 40 µmol/L of telmisartan for 24, 48, and 72 h. Cell proliferation was determined by MTT assay. (b) MMP-9 protein expression in THP-1 cells incubated with scratch-injured HUVECs supernatants for 1, 3, and 6 h. THP-1 cells in telmisartan group were pretreated with telmisartan for 1 h before HUVECs supernatants treatment. (c) Quantitative data for (b). (d) ERK1/2 and Elk-1 phosphorylation and MMP-9 protein expression in control, injury, and telmisartan groups. Control group was THP-1 cultures treated with supernatants of HUVECs without injury, while injury group and telmisartan group were cultures treated with supernatants of HUVECs with scratch injury for 6 hours. Cultures of telmisartan group were pretreated with telmisartan for 1 h prior to HUVECs supernatants treatment. (e) Quantitative data for (d). Note: ∗P < 0.05 compared with control group; #P < 0.05 compared with injury group.
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fig6: Telmisartan suppresses MMP-9 expression by inhibiting Elk-1 phosphorylation in THP-1 cells induced by scratch-injured human umbilical vein endothelial cells (HUVECs) supernatants. (a) Growth inhibiting effects of telmisartan on THP-1 cells. THP-1 cells were treated with 1.25, 2.5, 5, 10, 20, and 40 µmol/L of telmisartan for 24, 48, and 72 h. Cell proliferation was determined by MTT assay. (b) MMP-9 protein expression in THP-1 cells incubated with scratch-injured HUVECs supernatants for 1, 3, and 6 h. THP-1 cells in telmisartan group were pretreated with telmisartan for 1 h before HUVECs supernatants treatment. (c) Quantitative data for (b). (d) ERK1/2 and Elk-1 phosphorylation and MMP-9 protein expression in control, injury, and telmisartan groups. Control group was THP-1 cultures treated with supernatants of HUVECs without injury, while injury group and telmisartan group were cultures treated with supernatants of HUVECs with scratch injury for 6 hours. Cultures of telmisartan group were pretreated with telmisartan for 1 h prior to HUVECs supernatants treatment. (e) Quantitative data for (d). Note: ∗P < 0.05 compared with control group; #P < 0.05 compared with injury group.

Mentions: Telmisartan was reported to reduce restenosis after stenting [28]. We aimed to investigate whether telmisartan inhibits MMP-9 expression via the ERK1/2/Elk-1 pathway. Firstly, we used an MTT assay to select the optimum concentration of telmisartan. The results showed that telmisartan inhibited cell growth in a dose- and time-dependent manner (Figure 6(a)). And low concentration of telmisartan (≤10 µmol/L) affects the cell growth smaller. THP-1 cell growth approached a plateau above this 10 µmol/L. Thus, we choose 10 µmol/L as the concentrations of telmisartan for the next experiments.


Serum Levels of IL-1 β , IL-6, TGF- β , and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting.

Zhang R, Jiang F, Chen CS, Wang T, Feng J, Tao T, Qin X - Mediators Inflamm. (2015)

Telmisartan suppresses MMP-9 expression by inhibiting Elk-1 phosphorylation in THP-1 cells induced by scratch-injured human umbilical vein endothelial cells (HUVECs) supernatants. (a) Growth inhibiting effects of telmisartan on THP-1 cells. THP-1 cells were treated with 1.25, 2.5, 5, 10, 20, and 40 µmol/L of telmisartan for 24, 48, and 72 h. Cell proliferation was determined by MTT assay. (b) MMP-9 protein expression in THP-1 cells incubated with scratch-injured HUVECs supernatants for 1, 3, and 6 h. THP-1 cells in telmisartan group were pretreated with telmisartan for 1 h before HUVECs supernatants treatment. (c) Quantitative data for (b). (d) ERK1/2 and Elk-1 phosphorylation and MMP-9 protein expression in control, injury, and telmisartan groups. Control group was THP-1 cultures treated with supernatants of HUVECs without injury, while injury group and telmisartan group were cultures treated with supernatants of HUVECs with scratch injury for 6 hours. Cultures of telmisartan group were pretreated with telmisartan for 1 h prior to HUVECs supernatants treatment. (e) Quantitative data for (d). Note: ∗P < 0.05 compared with control group; #P < 0.05 compared with injury group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig6: Telmisartan suppresses MMP-9 expression by inhibiting Elk-1 phosphorylation in THP-1 cells induced by scratch-injured human umbilical vein endothelial cells (HUVECs) supernatants. (a) Growth inhibiting effects of telmisartan on THP-1 cells. THP-1 cells were treated with 1.25, 2.5, 5, 10, 20, and 40 µmol/L of telmisartan for 24, 48, and 72 h. Cell proliferation was determined by MTT assay. (b) MMP-9 protein expression in THP-1 cells incubated with scratch-injured HUVECs supernatants for 1, 3, and 6 h. THP-1 cells in telmisartan group were pretreated with telmisartan for 1 h before HUVECs supernatants treatment. (c) Quantitative data for (b). (d) ERK1/2 and Elk-1 phosphorylation and MMP-9 protein expression in control, injury, and telmisartan groups. Control group was THP-1 cultures treated with supernatants of HUVECs without injury, while injury group and telmisartan group were cultures treated with supernatants of HUVECs with scratch injury for 6 hours. Cultures of telmisartan group were pretreated with telmisartan for 1 h prior to HUVECs supernatants treatment. (e) Quantitative data for (d). Note: ∗P < 0.05 compared with control group; #P < 0.05 compared with injury group.
Mentions: Telmisartan was reported to reduce restenosis after stenting [28]. We aimed to investigate whether telmisartan inhibits MMP-9 expression via the ERK1/2/Elk-1 pathway. Firstly, we used an MTT assay to select the optimum concentration of telmisartan. The results showed that telmisartan inhibited cell growth in a dose- and time-dependent manner (Figure 6(a)). And low concentration of telmisartan (≤10 µmol/L) affects the cell growth smaller. THP-1 cell growth approached a plateau above this 10 µmol/L. Thus, we choose 10 µmol/L as the concentrations of telmisartan for the next experiments.

Bottom Line: Telmisartan could reduce inflammation.In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months.MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

ABSTRACT
Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS). Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs) that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor) attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

No MeSH data available.


Related in: MedlinePlus