The stimulation of arginine transport by TNFalpha in human endothelial cells depends on NF-kappaB activation

In human saphenous vein endothelial cells (HSVECs), tumor necrosis factor-\u3b1 (TNF\u3b1) and bacterial lipopolysaccharide (LPS), but neither interferon \u3b3 (IFN\u3b3) nor interleukin 1\u3b2 (IL-1\u3b2), stimulate arginine transport. The effects of TNF\u3b1 and LPS are due solely to the enhancement of system y+ activity, whereas system y+L is substantially unaffected. TNF\u3b1 causes an increased expression of SLC7A2/CAT-2B gene while SLC7A1/CAT-1 expression is not altered by the cytokine. The suppression of PKC-dependent transduction pathways, obtained with the inhibitor chelerytrhine, the inhibitor peptide of PKC\u3b6 isoform, or chronic exposure to phorbol esters, does not prevent TNF\u3b1 effect on arginine transport. Likewise, ERK, JNK, and p38 MAP kinases are not involved in the cytokine effect, since arginine transport stimulation is unaffected by their specific inhibitors. On the contrary, inhibitors of NF-\u3baB pathway hinder the increase in CAT2B mRNA and the stimulation of arginine uptake. These results indicate that in human endothelial cells the activation of NF-\u3baB pathway mediates the TNF\u3b1 effects on arginine transport