The result is consistent with the report that overexpression of HO- 1 prevented adhesion molecules expression and leukocytes to activated endothelial cells,. Our results suggested that the induction of HO-1 by NaHS may function in a negative feedback manner to down-regulate adhesion molecules expression, as reported by Paine A. MAPK and NF-kB are key players in intracellular signaling pathways in response to inflammatory stimuli and CX546 required for adhesion molecules expression,. Therefore, to further investigate the molecular mechanism responsible for the inhibitory effect of NaHS on expression of adhesion molecules, we examined the effect of NaHS on NF-kB and MAPK activation. Our results demonstrated that NaHS potently suppressed TNF-a-stimulated phosphorylation and nuclear translocation of NF-kB p65 in HUVEC. Consistent with previous report, phosphorylation and nuclear translocation of NF-kB p65 were found to be the main components of TNF-a-induced NF-kB activaton in HUVEC. The results suggested that the inhibition of NF-kB activaton by NaHS is mediated by modulation of upstream signaling pathway involved in NF-kB activation. Numerous natural components and therapeutic agents have been shown to inhibit NF-kB DCB activation by preventing IkBa degradation. Our data indicate that NaHS not only inhibited the IkBa degradation, but also attenuated the nuclear translocation of NF-kB. This provides evidence that H2S can attenuate TNF-a-induced NF-kB activation, as previously reported,. However, the kinase responsible for IkBa degradation has not been identified. There are also studies suggesting that MAPK is involved in the regulation of NF-kB activation in TNF-a-induced endothelial cells. Here, we demonstrated that NaHS inhibited TNF-a-stimulated p38 MAPK signal pathway in HUVEC, but had little effect on ERK1/2 or JNK1/2 phosphorylation. Although ERK1/2 mainly mediates cellular responses to hormones and growth factors, JNK1/2 and p38 are primarily activated by stress-related stimuli. Inhibition of p38 MAPK markedly inhibited the NF-kB activation and subsequent the expression of adhesion molecules in TNF-astimulated endothelial cells. Meanwhile, inhibition and genetic deficiency of p38 MAPK also contribute to induce HO-1 expression, which functions in a negative feedback manner to inhibit NF-kB activation.