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  • Title: Vasoactive intestinal peptide enhances TNF-α-induced IL-6 and IL-8 synthesis in human proximal renal tubular epithelial cells by NF-κB-dependent mechanism.
    Author: Huang L, Tang Y, Qin J, Peng Y, Yuan Q, Zhang F, Tao L.
    Journal: Inflammation; 2012 Jun; 35(3):1154-60. PubMed ID: 22207455.
    Abstract:
    Vasoactive intestinal polypeptide (VIP) is a 28-amino acid neuropeptide with vasodilator, bronchodilator, and anti-inflammatory effects. But little is known about its pro-inflammatory effects. We investigated the effect of VIP on the secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8), two pro-inflammatory cytokines, in TNF-α-activated proximal renal tubular epithelial cell line (HK-2 cells). Cultured HK-2 cells were treated with TNF-α in the presence or absence of VIP with a dose range from 1 to 100 nM, followed by analysis of pro-inflammatory cytokines (IL-6 and IL-8) induction and their signal events including activation of the NF-κB pathway. We report here that tumor necrosis factor-α (TNF-α) increased IL-6 and IL-8 production, and that these effects were potentiated by VIP at 10 nM in HK-2 cells. However, VIP at 1 and 100 nM did not display this function. Consistent with these observations, we were able to show that VIP at 10 nM upregulated TNF-α-induced phosphorylation of IκB-α, leading to IκB-α degradation and the subsequent nuclear translocation of NF-κB. Furthermore, VIP-enhanced activation of NF-κB transcription activity was demonstrated using a NF-κB reporter construct upon transient transfection into HK-2 cells. These results strongly suggest that VIP synergistically enhances TNF-α-stimulated IL-6 and IL-8 synthesis via activating the NF-κB pathway in HK-2 cells.
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