t and work through the induction of TNF-a or they may act synergistically with TNF-a. Already in 1994, Zuckerman and coworkers showed that antibodies to TNF-a prevented the reduction of apoE in mouse macrophages treated with LPS or GM-CSF. They further showed that antibodies to IL-1a, IL-1b and IFN-c did not have the same effect. The fact that the results with TNF-a neutralization could here be reproduced with human cells using a therapeutically approved TNF-a blocker makes this approach amenable for testing also in humans. Interestingly, of the cytokines tested and shown to modulate apoE production, TNF-a is the only one produced by both T cells and monocytes. This suggests that TNF-a neutralization could be anticipated to prevent inflammation independent of whether it is caused by an overactivation of T cells or innate immune cells or both. As an attractive alternative to inhibiting TNF-a, therapy could potentially also be based on an upregulation of apoE production. The identification of factors which can modulate apoE in monocytes and macrophages would therefore be of great interest. If existing, such factor/s could help to change the balance towards a more anti-inflammatory state that may have a beneficial effect not only on atherosclerosis but also on several other conditions characterized by excessive inflammation. In contrast to monocytes and macrophages, we found that apoE secretion by hepatocytes was only marginally affected by inflammatory cytokines. The effect, which was only seen in ELISA, was manifested as a small but significant decrease of apoE in supernatants from HepgG2 cells after treatment with IFN-a or TNF-a but not IFN-c or LPS. Similar effects of TNF-a and also IL-1b on HepG2 cells have previously been reported by Song and et al who also, in concordance with our results on monocytes, did not see any inhibition with IL-6. The fact that we could 1685439 not observe the same effect in the ELISpot as in ELISA, demonstrates the differences in the two techniques with ELISpot providing the frequency of secreting cells, but with limited information about the amount produced by each cells whereas ELISA gives the concentration of a secreted analyte produced by a collective of cells. In conclusion, we have demonstrated that apoE ELISpot analysis of PBMC may provide a convenient model to investigate apoE Scutellarein production and regulation. Using this approach, we could confirm the suppressive effect of several known pro-inflammatory cytokines. In addition, we identified IFN-a as a potent inhibitor of apoE production whereas IL-6, generally considered as pro-inflammatory, had no such effect. Providing further support for a causal relationship between activated T cells and the induction of atherosclerosis 12750467 we could also show a clear reduction in apoE secretion in PBMC containing stimulated T cells. The observations made in this study support that apoE, having a central role as an anti-inflammatory molecule, constitutes a potential therapeutic target in atherosclerosis and other inflammatory-related diseases. of cofilin, LIMK and occludin into the cell monolayers confirmed their contribution to the transepithelial electrical resistance decrease. Finally, exposure of monolayers 
to capsaicin augmented the paracellular passage of both charged and uncharged compounds, as well as of insulin, indicating that capsaicin can be employed to modulate epithelial permeability. Our results demonstrate that capsaicin induces TJ opening through a unique mechani