Thiram activates NF-kappaB and enhances ICAM-1 expression in human microvascular endothelial HMEC-1 cells.

Thiram (TMTD) is a fungicidal and bactericidal agent used as antiseptic, seed disinfectant and animal repellent. In the light of known properties, thiram is considered to be used as an inhibitor of angiogenesis and/or inflammation. Since angiogenesis requires the growth of vascular endothelial cells we have used microvascular endothelial cell line HMEC-1 to elucidate the effect of thiram on normal and stimulated cells. We cultured HMEC-1 cells in the presence of thiram at low concentration (0.5 µg/mL or 2 µg/mL) (0.2 µM or 0.8 µM) or TNF-α (10 ng/mL) alone, and thiram together with TNF-α. TNF-α was used as a cytokine that triggers changes characteristic for inflammatory state of the cell. We carried out an in vitro study aimed at assessing generation of reactive oxygen species (ROS), activation of NF-κB, and expression of cell adhesion molecules ICAM-1, VCAM-1, PECAM-1. It was found that TMTD produced ROS and activated NF-κB. Activation of NF-κB was concurrent with an increase in ICAM-1 expression on the surface of HMEC-1 cells. ICAM-1 reflects intensity of inflammation in endothelial cell milieu. The expression of VCAM-1 and PECAM-1 on these cells was not changed by thiram. It was also found that stimulation of the HMEC-1 cells with the pro-inflammatory cytokine TNF-α caused activation of ICAM-1 and VCAM-1 expression with concomitant decrease of PECAM-1 cell surface expression above the control levels. Treatment with thiram and TNF-α changed cellular response compared with effects observed after treatment with TNF-α alone, i.e. further increase of ICAM-1 expression and impairment of the TNF-α effect on PECAM-1 and VCAM-1 expression. This study demonstrated that thiram acts as a pro-oxidant, and elicits in endothelial cell environment effects characteristic for inflammation. However, when it is present concurrently with pro-inflammatory cytokine TNF-α interferes with its action.

Kurpios-Piec D ，Grosicka-Maciąg E ，Woźniak K ，Kowalewski C ，Kiernozek E ，Szumiło M ，Rahden-Staroń I ... -  《-》

TNFR1-induced NF-kappaB, but not ERK, p38MAPK or JNK activation, mediates TNF-induced ICAM-1 and VCAM-1 expression on endothelial cells.

Zhou Z ，Connell MC ，MacEwan DJ 《CELLULAR SIGNALLING》

Chloroform extract of aged black garlic attenuates TNF-α-induced ROS generation, VCAM-1 expression, NF-κB activation and adhesiveness for monocytes in human umbilical vein endothelial cells.

Aged black garlic is a type of fermented garlic (Allium sativum) which has been used in Oriental countries for a long time because of various biological properties of garlic derivatives. The current study explored the potential of the chloroform extract of aged black garlic (CEABG) in attenuating the activities of adhesion molecules in tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). The study was performed on HUVECs that were pretreated with 30 μg/mL of CEABG before TNF-α treatment. Treatment of HUVECs with CEABG significantly inhibited TNF-α-induced reactive oxygen species (ROS) formation. HUVECs treated with CEABG showed markedly suppressed TNF-α-induced mRNA expression of VCAM-1, but little alteration in ICAM-1 and E-selectin mRNA expression. CEABG treatment also significantly decreased the TNF-α-induced cell surface and total protein expression of VCAM-1 without affecting ICAM-1 and E-selectin expression. In addition, treatment of HUVECs with CEABG markedly reduced THP-1 monocyte adhesion to TNF-α-stimulated HUVECs. Furthermore, CEABG significantly inhibited NF-κB transcription factor activation in TNF-α-stimulated HUVECs. The data provide new evidence of the antiinflammatory properties of CEABG that may have a potential therapeutic use for the prevention and treatment of vascular diseases such as atherosclerosis through mechanisms involving the inhibition of VCAM-1 expression and NF-κB activation in vascular endothelial cells.

Lee EN ，Choi YW ，Kim HK ，Park JK ，Kim HJ ，Kim MJ ，Lee HW ，Kim KH ，Bae SS ，Kim BS ，Yoon S ... -  《-》

Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells.

Kim SR ，Bae YH ，Bae SK ，Choi KS ，Yoon KH ，Koo TH ，Jang HO ，Yun I ，Kim KW ，Kwon YG ，Yoo MA ，Bae MK ... -  《-》

Regulation of adhesion molecules expression in TNF-α-stimulated brain microvascular endothelial cells by tanshinone IIA: involvement of NF-κB and ROS generation.

Pro-inflammatory cytokine-mediated expression of cell surface adhesion molecules plays a key role in endothelial cell injury, leading to vascular inflammation and the development of many cerebrovascular diseases. Thus, antiinflammatory agents targeting these adhesion molecules may represent potential drugs for the prevention and treatment of cerebrovascular diseases. The present study explored the effects of tanshinone IIA (Tan IIA), an active ingredient present in the Salvia miltiorrhiza root, on the expression of cellular adhesion molecules in TNF-α-stimulated brain microvascular endothelial cells (BMVECs). Treatment with Tan IIA was found to suppress the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), resulting in inhibition of TNF-α-induced adhesion of neutrophils to BMVECs in a dose-dependent manner. In addition, Tan IIA significantly inhibited TNF-α-induced production of reactive oxygen species (ROS), which was accompanied by decreased malondialdehyde (MDA) levels. Treatment with Tan IIA also inhibited nuclear factor-kappa B (NF-κB) activation. Together, these results suggest that Tan IIA regulates TNF-α-induced expression of VCAM-1 and ICAM-1 through inhibition of NF-κB activation and ROS generation in BMVECs.

Tang C ，Xue HL ，Bai CL ，Fu R ... -  《-》