anisomycin and Vasculitis

Sulforaphane (SFN), mainly derived from cruciferous vegetables, has received much attention for its cancer chemopreventive property. Though there have been a few epidemiological studies supporting its beneficial effect on cardiovascular diseases, much experimental evidence are still required to understand its mechanism. In this study, human vascular endothelial cell, a barrier of blood, was used as an in vitro model to investigate the protective effect of sulforaphane on inflammatory damage induced by lipopolysaccharide (LPS). The results showed that sulforaphane inhibited the expression of COX-2 and iNOS stimulated by lipopolysaccharide in a dose- and time-dependent manner. Moreover, sulforaphane suppressed the phosphorylation of ERK1/2, JNK, and p38 activated by lipopolysaccharide. Pretreatment with SB202190, the specific inhibitor of p38, abolished the expression of COX-2 induced by LPS. Likewise, SP600125, inhibitor of JNK, abrogated iNOS expression stimulated by LPS. Moreover, pretreatment with anisomycin (AM), an activator of p38 and JNK, instead of LPS, the expression of COX-2 and iNOS is still inhibited by sulforaphane. Interestingly, SFN significantly induced HO-1 and TR expression down-regulated by LPS. Taken together, these data indicated that sulforaphane exhibited the protective role against the inflammatory injury in vascular endothelia cells, through inactivating p38 MAPK and JNK, as well as inducing phase 2 enzymes.

Topics: Anisomycin; Anthracenes; Anticarcinogenic Agents; Blotting, Western; Cell Line; Cyclooxygenase 2; Drug Antagonism; Endothelium, Vascular; Enzyme Inhibitors; Heme Oxygenase-1; Humans; Imidazoles; Isothiocyanates; Lipopolysaccharides; Membrane Proteins; Mitogen-Activated Protein Kinases; Neoplasm Proteins; Nitric Oxide Synthase Type II; Phosphorylation; Pyridines; Sulfoxides; Thiocyanates; Vasculitis