When MaR1 was incubated with monocytes alone, we also saw an inhibition of the adhesive effect, which might imply that MaR1 interferes with monocyte function. Flow-cytometry based analyses showed that MaR1 causes a 20–30% reduction in cell surface E-selectin expression, which is involved with “rolling” phenomenon of monocytes that precedes firm adhesion. Surprisingly, we did not see any significant inhibition of cell surface expression of VCAM-1 and ICAM-1 in EC and VSMC by MaR1. Investigations are underway in our lab in order to better characterize the mechanisms of reduced adhesion in the presence of MaR1, looking at multiple pathways that may affect monocyte interactions to EC and VSMC. TNF-a causes generation of reactive oxygen species in endothelial and smooth muscle cells primarily through activation of NADPH-oxidase 4. Other cell-specific isoforms of NOX, like NOX-1 and NOX-2 are also involved with TNF-a-induced ROS generation but to a much lesser extent compared to NOX-4. Two recent studies show RvD1 and RvE1 to reduce ROS production in macrophages, however to our knowledge, no study has examined the Everolimus mTOR inhibitor effects of MaR1 on ROS generation in EC or VSMC. Our results show MaR1 to attenuate ROS production, associated with reduced NOX protein expression in both cell types. As ROS is known to play a potentially detrimental role in inflammation, the observed beneficial effects of MaR1 could be partially linked to attenuation of the ROS response. Additional studies involving mRNA and protein expression of components of NOX-4 enzyme complex, NOX-4 enzyme activity, and characterization of ROS species are under way to further elucidate mechanisms of ROS attenuation. TNF-a activates multiple pro-inflammatory transcription factors in EC and VSMC that result in gene transcription and release of the mediators in the extracellular milieu, that act in a paracrine and autocrine fashion to modulate the inflammatory responses. We investigated the effects of MaR1 on extracellular release of 40 different inflammatory mediators in TNF-a activated EC and VSMC 18 hr post TNF-a, and found MaR1 to attenuate a number of the mediators including chemokines and chemoattractants like Interferon gamma induced protein-10, MCP-1, RANTES, MIP-1b, IL-8, Eotaxin-2, IL-16 and cytokines such as GM-CSF and IL-3 which are involved with proliferation and maturation of cells of myeloid lineage. Interestingly, MaR1 also attenuated PDGF-BB release from endothelial cells, an important regulator of VSMC proliferation and migration. MaR1 has been shown in vivo to block NF-kB activation in colonic tissues in a murine colitis model, however MaR1 was found to have no inhibitory effect on NFkB activation in human bronchial epithelial cells. Our results show a strong inhibitory effect of MaR1 on NF-kB activation in both cell types, involving several key steps involved with NF-kB activation including phosphorylation of IKK and IkB-a degradation. RvD1 and RvE1 receptors have been identified.