Investigation of the Inhibitory Mechanisms of N-hydroxycinnamoylphenalkylamides Analogues and Aristolochic Acid on MCP-1-Activated Monocytic cells

• Main Authors: Hsin-Yu Wang, 王欣玉
• Other Authors: 蕭哲志
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/03473602361414176406

碩士 === 臺北醫學大學 === 醫學科學研究所 === 97 === In the human innate immune system, the monocytes are the key cellular elements and serve as a critical line of defense. Inflammatory monocytes respond rapidly to microbial stimuli by secreting cytokines and antimicrobial factors, express the CCR2 chemokine receptor, and traffic to sites of microbial infection in response to monocyte chemoattractnat protein (MCP-1) secretion. On the other hand, the monocytes also can differentiate to macrophages and proceed a more powerful, long-term immunoreaction. When normal regulatory mechanisms fail, the monocyte is also responsible for immunologically induced many physiological and pathological changes, like atherosclerosis, rheumatoid arthritis (RA) and cancer. In in vitro invasion and migration assay, we found that N-hydroxycinnamoylphenalkylamides analogues (EK5 and EK8) and Aristolochic acid (AsA) showed obviously inhibitory effect on MCP-1-induced monocyte invasion and migration. The MEK inhibitor PD98059 and PI3K inhibitor LY294002 also inhibited MCP-1-induced monocyte invasion, so monocyte invasion might be regulated by ERK1/2 and PI3K signaling pathway. We also found AsA and EK5 might inhibit MCP-1-induced monocyte tethering (rolling) to firm adhesion via integrin activation and MMP-9 activity by affecting Akt signaling pathway. And AsA might inhibit MCP-1-induced monocyte ??1 integrin activation and actin rearrangement by affecting ERK1/2 signaling pathway. But EK8 had no effect on Akt and ERK1/2 signaling.