Ferulic acid attenuates adhesion molecule expression in gamma-radiated human umbilical vascular endothelial cells.
Radiation induces an important inflammatory response in the irradiated organs, characterized by leukocyte infiltration and vascular changes. Since adhesion molecules play an important role in facilitating the immune response at the inflammation sites, interfering with the expression of these molecules may be an important therapeutic target of radiation induced inflammation. Many adhesion molecules such as intercellular cell adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) have been identified in radiation. Ferulic acid (FA), an effective radioprotector during radiotherapy, is widely used in endothelium protection. The present study examined the effect of FA on the induction of adhesion molecules by gamma-radiation and the mechanisms of its effect in gamma-irradiated human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 18 h with FA and then exposed to 10 Gy radiation. The result of cell adhesion assay showed FA inhibited radiation-induced U937 adhesion to HUVECs. FA prevented induction of ICAM-1 and VCAM-1 expression in a concentration-dependent manner after stimulation with radiation at the level of mRNA and protein. Inhibitors of the extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways were used to determine which pathway was involved in FA action; the result showed that the inhibitory effect of FA on adhesion molecule expression was mediated by the blockade of JNK. FA appears to be a potential therapeutic agent for treating various inflammatory disorders including radiation induced inflammation.
Ma
Zeng-Chun
ZC
Beijing Institute of Radiation Medicine, Tai-Ping Road 27, Beijing 100850, PR China.
Hong
Qian
Q
Wang
Yu-Guang
YG
Tan
Hong-Ling
HL
Xiao
Cheng-Rong
CR
Liang
Qian-De
QD
Cai
Shao-Hua
SH
Gao
Yue
Y
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003373:Coumaric Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000528:radiation effects; D005720:Gamma Rays; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003373:Coumaric Acids; D010936:Plant Extracts; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C004999:ferulic acid; D048031:JNK Mitogen-Activated Protein Kinases