Περίληψη:
Prothymosin alpha (ProTα) is an acidic polypeptide associated both with cell proliferation and immune regulation. Although ProTα's immunomodulating activity is well established at cellular level, limited information is available regarding the signaling pathways triggered by ProTα. Using 2-DE proteomic technology, we investigated changes in protein expression of ProTα-stimulated peripheral blood mononuclear cells (PBMC) in the course of a 3-day incubation. Using healthy donor- and cancer patient-derived PBMC, 12 gels were studied, identifying 53 differing protein spots via PMF comparison analysis. Among others, we identified interleukin-1 receptor-associated kinase 4, heat-shock protein 90, lipocalin 2, ribophorin 1, eukaryotic elongation factor 2, 14-3-3 protein, L-plastin, and MX2 protein, all of which were found to be overexpressed upon ProTα activation. Based on the physiological role of upregulated proteins, we propose the following model for ProTα's immunological mode of action: on day 1, ProTα triggers monocyte activation, possibly via toll-like receptor signaling, and enhances antigen presentation, consequently promoting and stabilizing monocyte-T-cell immune synapse; on day 2, activated monocytes produce interleukin (IL)-1, while T-cell receptor triggering promotes T-cell proliferation and IL-2 production; finally, on day 3, ProTα-activated PBMC express proteins related to adhesion and cytotoxic effector functions, both contributing to the increase of their lytic activity. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
Συγγραφείς:
Skopeliti, M.
Kratzer, U.
Altenberend, F.
Panayotou, G.
Kalbacher, H.
Stevanovic, S.
Voelter, W.
Tsitsilonis, O.E.
Λέξεις-κλειδιά:
heat shock protein; heat shock protein 90; interleukin 1 receptor associated kinase 4; interleukin 2; lipocalin; prothymosin alpha; ribophorin I; T lymphocyte receptor, article; cancer; cell activation; cell adhesion; cytotoxicity; human; immunomodulation; mononuclear cell; priority journal; protein analysis; protein expression; proteomics, Electrophoresis, Gel, Two-Dimensional; Female; Humans; Leukocytes, Mononuclear; Lymphocyte Activation; Ovarian Neoplasms; Protein Precursors; Proteins; Proteomics; Reference Values; Signal Transduction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thymosin, Eukaryota
