Studies On Molecular Targets Of Non-classical Anti-Inflammatory Drugs

Objectives To investigate the molecular mechanisms of anti-inflammatory action of drugs, some essential physiopathologic links for the adhesion of leukocytes to vascular endothelial cells and/or keratinocytes, and angiogenesis as well were to be imitated in vitro and then the intervention tests of drugs or compounds were to be performed. To aim at establishing some experimental models and methods for pharmacodynamic screening in the field of anti-inflammatory or anti-angiogenesis agents and to service as reevaluation of known drugs and the screening of related pharmacological activity of probably related compounds and to discover new drugs as well.Methods Three kinds of cell or cell strain were cultured in vitro, then the different inducers and drugs or compounds were added, respectively. The pharmacological activities of thalidomide (Thd), dapsone (DDS), indomethacin (IND), clobetasol prapionate (CP), which were known as anti-inflammatory or antiangiogenesis drugs, as well as triptolide (T₀) and ABC, which were related compounds with possible anti-inflammatory activity were detected. The levels of molecules including intercellular adhesion molecule-1 (1CAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), interferon gamma (IFN- γ), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) were determined. Total RNA was isolated from cells cultured in vitro, reverse transcriptase polymerase chain reaction (RT-PCR) and Northern Blotting were used to determine the effects of these drugs or compounds on these molecules at the transcriptional level. In addition, LFN- γ protein levels in supematants of cells cultured in vitro were assayed by ELISA.Results I. Semi-quantitative RT-PCR measurements showed that ICAM-1 was...