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Role of Cortisol and Dehydroepiandrosterone on RACK1/PKC Signalling and Consequences in Immunosenescence

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Handbook of Immunosenescence

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Abstract

Over the past 15 years, it was demonstrated that defective protein kinase C (PKC) signal transduction machinery correlates to the decline of immune functions associated with aging. Experimental evidence suggest that altered PKC signalling results in impaired response to lipopolisaccaride (LPS) stimulation and cytokine release. Such defective signalling is due to reduced expression of receptor for activated C kinase 1 (RACK1) and to age-related alteration of the hormonal balance between cortisol and dehydroepiandrosterone (DHEA): cortisol levels remain substantially unchanged while DHEA levels decline with aging. These aspects are particularly relevant for the functional PKC signalling system because DHEA administration in vivo and in vitro in aged animals and in human cells can reestablish the levels of RACK1 and thus the function of the PKC signalling cascade. There is also evidence that cortisol and DHEA have opposite effect on the transcriptional regulation of the gene encoding for RACK1 and known as GNB2L1. At transcriptional level, cortisol has a peculiar function of a negative regulator of the RACK1 promoter, while the effect of DHEA seems to derive from a complex influence on the functions and post-transcriptional regulation of the glucocorticoid receptor (GR). Here we discuss the role of PKC/RACK1 signalling in the context of immune cells and immunosenescence also focusing on the role of cortisol and DHEA in the regulation of RACK1 expression.

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Authors and Affiliations

  1. Dipartimento di Scienze del Farmaco, Università degli Studi di Pavia, Pavia, Italy

    E. Buoso, Mm. Serafini, M. Galasso, M. Ronfani, L. Poloni, C. Lanni & M. Racchi

  2. Department of Environmental Science and Policy, Università degli Studi di Milano, Milan, Italy

    E. Corsini

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  1. E. Buoso
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  2. Mm. Serafini
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  3. M. Galasso
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  4. M. Ronfani
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  5. L. Poloni
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  6. C. Lanni
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  7. E. Corsini
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  8. M. Racchi
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Corresponding author

Correspondence to M. Racchi .

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Editors and Affiliations

  1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Dept. of Medicine, Sherbrooke, QC, Canada

    Tamas Fulop

  2. Dept of Experimental Pathology, University of Bologna, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, Tokyo, Japan

    Katsuiku Hirokawa

  4. Center for Medical Research, University of Tübingen, Tübingen, Germany

    Graham Pawelec

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Buoso, E. et al. (2019). Role of Cortisol and Dehydroepiandrosterone on RACK1/PKC Signalling and Consequences in Immunosenescence. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_116-1

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  • DOI: https://doi.org/10.1007/978-3-319-64597-1_116-1

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  • Print ISBN: 978-3-319-64597-1

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