Inhibitory effects of clotrimazole on TNF-α-induced adhesion molecule expression and angiogenesis

Abstract

Cell adhesion molecules play a pivotal role in chronic inflammation and pathological angiogenesis. In the present study, we investigated the inhibitory effects of clotrimazole (CLT) on tumor necrosis factor (TNF)-alpha-induced changes in adhesion molecule expression. CLT dose-dependently inhibited monocyte chemoattractant protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expressions in TNF-alpha-stimulated HT29 colonic epithelial cells. This inhibitory action of CLT correlated with a significant reduction in TNF-alpha-induced adhesion of monocytes to HT29 cells, which was comparable to the inhibitory effects of anti-ICAM-1 and VCAM-1 monoclonal antibodies on monocyte-epithelial adhesion. These inhibitory actions of CLT were, at least in part, attributable to the inhibition of redox sensitive NF-kappaB activation, as CLT inhibited TNF-alpha-induced ROS generation as well as NF-kappaB nuclear translocation and activation in HT29 cells. Furthermore, the inhibition of TNF-alpha-induced monocyte adhesion was also mimicked by the specific NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). Inflammatory mediators including TNF-alpha have known to promote angiogenesis, which in turn further contributes to inflammatory pathology. Therefore, we additionally evaluated whether CLT modulates TNF-alpha-induced angiogenesis using in vivo chick chorioallantoic membrane (CAM) assay. The CAM assay showed that CLT dose-dependently attenuated TNF-alpha-induced angiogenesis, and the effect was correlated with decreased inflammation of the CAM tissue. In conclusion, our results suggest that CLT can inhibit TNF-alpha-triggered expression of adhesion molecules, ICAM-1 and VCAM-1, and angiogenesis during inflammation.

Differential Cytokine Responses in Human and Mouse Lymphatic Endothelial Cells to Cytokinesin Vitro

“…For example, TNF-a can induce BEC inflammation and edema, and TNF-a suppression enhances lymphangiogenesis. 22 Although cytokines such as TNF-a participate in inflammatory angiogenesis in several clinical conditions, [23][24][25] cytokines may also regulate lymphatic responses, and play roles in different phases of inflammation that are not yet well understood. To overcome limitations encountered with in vivo lymphangiogenesis models, we used human and mouse LECs to study lymphatic responses to inflammatory cytokines.…”

Lactobacillus plantarum Lipoteichoic Acid Alleviates TNF-α-Induced Inflammation in the HT-29 Intestinal Epithelial Cell Line

“…4C). Since the adhesion of monocytes to IECs represents the expression of adhesion molecules and inflammation of both cells (Lee et al, 2010;Thapa et al, 2009), we examined whether pLTA inhibits the rhTNF-α-induced adhesion of monocytes to colon epithelial cells. As shown in Fig.…”

Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-α production and its signaling

“…TNF-α-induced adhesion of monocytes to colon epithelial cells represents an in vitro model of intestinal inflammation (Thapa et al, 2009). As shown in Figures 4A and 4B, TNF-α significantly enhanced the adhesion of fluorescence-labeled U937 premonocytic cells to HT-29 cells.…”