The stimulation of arginine transport by TNFα in human endothelial cells depends on NF-κB activation

• Published in: Biochimica et biophysica acta. Biomembranes Vol. 1664; no. 1; pp. 45 - 52
• Main Authors: Visigalli, Rossana, Bussolati, Ovidio, Sala, Roberto, Barilli, Amelia, Rotoli, Bianca Maria, Parolari, Alessandro, Alamanni, Francesco, Gazzola, Gian C, Dall'Asta, Valeria
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.07.2004
• Subjects: CAT transporter; NFκB; SLC7 gene; TNFα; IFNγ; TNFα; NFκB; PDTC; M199; CFPD; MG132; PPM-18; CAPE; IL-1β; SB203580; LPS; SP600125; SLC7 gene; NOS; DRB; FBS; NEM; PD98059; HSVECs; CAT transporter; EBSS; HUVECs
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2004.04.001

In human saphenous vein endothelial cells (HSVECs), tumor necrosis factor-α (TNFα) and bacterial lipopolysaccharide (LPS), but neither interferon γ (IFNγ) nor interleukin 1β (IL-1β), stimulate arginine transport. The effects of TNFα and LPS are due solely to the enhancement of system y + activity, whereas system y +L is substantially unaffected. TNFα  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 PKCζ isoform, or chronic exposure to phorbol esters, does not prevent TNFα 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-κB 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-κB pathway mediates the TNFα effects on arginine transport.