title: Carnosol inhibits cell adhesion molecules and chemokine expression by tumor necrosis factor-α in human umbilical vein endothelial cells through the nuclear factor-κB and mitogen-activated protein kinase pathways.
abstract: Inflammatory bowel diseases (IBD) are gastrointestinal disorders associated with chronic inflammatory processes. Carnosol has been demonstrated to possess anti-inflammatory properties. This study examined the suppressive effect of carnosol on the expression of cell adhesion molecules (CAMs) and chemokines in human umbilical vein endothelial cells (HUVECs) and the possible underlying mechanism. The effect of carnosol on CAM and chemokine expression in HUVECs was identified by western blotting and ELISA, respectively. nuclear factor (NF)-κB activation of HUVECs was analyzed using the TransAM NF-κB Family kit. The effect of carnosol on the tumor necrosis factor (TNF)-α-induced activation of the NF-κB and mitogen-activated protein kinase (MAPK) pathways, and was subsequently analyzed using western blotting. Carnosol not only inhibited TNF-α-induced protein expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin in HUVECs, but also suppressed interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, carnosol inhibited the TNF-α-induced phosphorylation of p-65 and IκB-α, as well as the activation of NF-κB. The same result was observed in TNF-α-stimulated phosphorylation of ERK1/2 and p-38. It was demonstrated that carnosol inhibited TNF-α-induced CAM and chemokine expression in HUVECs. The underlying mechanism may be associated with the blocking of the NF-κB and MAPK pathways. These results indicate that carnosol may be a novel therapeutic agent for targeting endothelial cells in IBDs.
authors: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangdong Gastrointestinal Hospital, Guangzhou, Guangdong 510655, P.R. China.
authors: Hui
authors: H
authors: Yao
authors: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangdong Gastrointestinal Hospital, Guangzhou, Guangdong 510655, P.R. China.
authors: Yufeng
authors: Y
authors: Chen
authors: Laboratory of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Longjuan
authors: L
authors: Zhang
authors: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangdong Gastrointestinal Hospital, Guangzhou, Guangdong 510655, P.R. China.
authors: Xiaosheng
authors: X
authors: He
authors: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangdong Gastrointestinal Hospital, Guangzhou, Guangdong 510655, P.R. China.
authors: Xiaowen
authors: X
authors: He
authors: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangdong Gastrointestinal Hospital, Guangzhou, Guangdong 510655, P.R. China.
authors: Lei
authors: L
authors: Lian
authors: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangdong Gastrointestinal Hospital, Guangzhou, Guangdong 510655, P.R. China.
authors: Xiaojian
authors: X
authors: Wu
authors: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangdong Gastrointestinal Hospital, Guangzhou, Guangdong 510655, P.R. China.
authors: Ping
authors: P
authors: Lan
mesh_terms: D045784:Abietanes / Q000008:administration & dosage*; D002448:Cell Adhesion / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D045784:Abietanes; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C068623:carnosol; D020928:Mitogen-Activated Protein Kinases