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Vasoactive intestinal peptide induces cell cycle arrest and regulatory functions in human T cells at multiple levels

Opened Access Vasoactive intestinal peptide induces cell cycle arrest and regulatory functions in human T cells at multiple levels

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Autor: Anderson, Per
Gonzalez-Rey, Elena
Fecha: 2010-05
Tipo de documento: Artículo
Resumen: Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory neuropeptide that, by inhibiting Th1-driven responses and inducing the emergence of regulatory T cells (Treg), has been proven successful in the induction of tolerance in various experimental models of autoimmune disorders. Here, we investigate the molecular mechanisms involved in VIP-induced tolerance. VIP treatment in the presence of T-cell receptor (TCR) signaling and CD28 costimulation induced cell cycle arrest in human T cells. VIP blocked G1/S transition and inhibited the synthesis of cyclins D3 and E and the activation of the cyclin-dependent kinases (CDKs) cdk2 and cdk4. This effect was accompanied by maintenance of threshold levels of the CDK inhibitor p27kip1 and impairment of phosphatidylinositol 3-kinase (PI3K)-Akt signaling. Inhibition of interleukin 2 (IL-2) transcription and downregulation of signaling through NFAT, AP-1, and Ras-Raf paralleled the VIPinduced cell cycle arrest. Noteworthy from a function...
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Tamaño: 2.262Mb
Formato: PDF

URI: http://hdl.handle.net/11441/61339

DOI: 10.1128/MCB.01282-09

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