Research Papers: Gerotarget (Focus on Aging):

Immunostimulatory effects of RACK1 pseudosubstrate in human leukocytes obtained from young and old donors

Emanuela Corsini _, Valentina Galbiati, Antonella Pinto, Annalisa Davin, Letizia Polito, Antonio Guaita and Marco Racchi

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Oncotarget. 2015; 6:6524-6534. https://doi.org/10.18632/oncotarget.3002

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Emanuela Corsini1, Valentina Galbiati1, Antonella Pinto2, Annalisa Davin3, Letizia Polito3, Antonio Guaita3, Marco Racchi2

1Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano, Milan, Italy

2Department of Drug Sciences - Pharmacology, University of Pavia, Pavia, Italy

3“Golgi Cenci” Foundation, Abbiategrasso, Italy

Correspondence to:

Emanuela Corsini, e-mail: [email protected]

Keywords: PKC, immunosenescence, cytokines, whole blood assay, signal transduction

Received: November 10, 2014     Accepted: December 21, 2014     Published: March 12, 2015


Aims of this study were to investigate the ability of RACK1 pseudosubstrate alone or in combination with classical immune stimuli to activate human leukocytes, and to restore age-associated immune defects.

A total of 25 donors (17 old donors, 77–79 yrs; 8 young donors, 25–34 yrs) were enrolled. To evaluate the effect of RACK1 pseudosubstrate on cytokine production and CD86 expression the whole blood assay was used. Cultures were treated with RACK1 pseudosubstrate in the presence or absence of lipopolysaccharide (LPS) or phytohaemagglutinin (PHA) and incubated for 24 h or 48 h for LPS-induced CD86 expression, TNF-α, IL-6, IL-8, IL-10 production, and PHA-induced IL-4, IL-10, IFN-γ, respectively. RACK1 pseudosubstrate alone induced IL-6, IL-8, and CD86 expression in both young and old donors, and IFN-γ in old donors. In combination with LPS an increase in IL-8, IL-10 and TNF-α was observed, also resulting in restoration of age-associated defective production, while no changes in the other parameters investigated were found.

Even if based on a small sample size, these results suggest the possibility to by-pass some of age-associated immune alterations, which may be beneficial in situations were natural immune stimulation is required, and highlight a different role of PKCβ in immune cells activation.

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