Age-related decline in RACK-1 expression in human leukocytes is correlated to plasma levels of dehydroepiandrosterone

Emanuela Corsini, Marco Racchi, Elena Sinforiani, Laura Lucchi, Barbara Viviani, Gian Enrico Rovati, Stefano Govoni, Corrado L. Galli, Marina Marinovich

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Aging is associated with remodeling of the immune system, contributing to increased incidence of infections, autoimmune diseases, and cancer among the elderly. Alterations in several signal transduction pathways have been reported to play an important role in immunosenescence. We show that peripheral blood leukocytes obtained from old donors (≥65 years) have a significantly reduced expression of receptor for activated C kinase 1 (RACK-1), a protein required for protein kinase C (PKC)-β signaling, as compared with young donors (≤40 years), both in males and females. The decline in RACK-1 immunoboth in reactivity was age-related (Spearman correlation, r=-0.278, P=0.012). All leukocyte subpopulations, namely lympho-monocytes, granulocytes, and B and T cells, showed a similar defect. We also observed a direct correlation between circulating dehydroepiandrosterone (DHEA) and RACK-1 expression in leukocytes (Spearman correlation, r=0.388, P=0.001). Furthermore, in vitro treatment with DHEA resulted in increased RACK-1 expression in leukocytes and lymphocyte proliferation, confirming the role of this hormone in the modulation of its expression and immune functions. A relevant consequence of RACK-1-reduced expression was the observation that release of tumor necrosis factor α following lipopolysaccharide challenge and mitogen-induced lymphocye proliferation, which involves PKC-β activation, was significantly reduced in elderly subjects. Overall, our findings contribute to the understanding of the complex process of immunosenescence and identify age-related loss in immunological responses as partially associated with decreased RACK-1 expression.

Original languageEnglish
Pages (from-to)247-256
Number of pages10
JournalJournal of Leukocyte Biology
Volume77
Issue number2
DOIs
Publication statusPublished - Feb 2005

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Dehydroepiandrosterone
Leukocytes
Protein Kinase C
Tissue Donors
Mitogens
Granulocytes
Autoimmune Diseases
Lipopolysaccharides
Monocytes
Immune System
Signal Transduction
B-Lymphocytes
Tumor Necrosis Factor-alpha
receptors for activated C kinase
Hormones
Lymphocytes
T-Lymphocytes
Incidence
Infection
Neoplasms

Keywords

  • Aging
  • Cytokines
  • Immunosenescence
  • Protein kinase
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

Cite this

Age-related decline in RACK-1 expression in human leukocytes is correlated to plasma levels of dehydroepiandrosterone. / Corsini, Emanuela; Racchi, Marco; Sinforiani, Elena; Lucchi, Laura; Viviani, Barbara; Rovati, Gian Enrico; Govoni, Stefano; Galli, Corrado L.; Marinovich, Marina.

In: Journal of Leukocyte Biology, Vol. 77, No. 2, 02.2005, p. 247-256.

Research output: Contribution to journalArticle

Corsini, E, Racchi, M, Sinforiani, E, Lucchi, L, Viviani, B, Rovati, GE, Govoni, S, Galli, CL & Marinovich, M 2005, 'Age-related decline in RACK-1 expression in human leukocytes is correlated to plasma levels of dehydroepiandrosterone', Journal of Leukocyte Biology, vol. 77, no. 2, pp. 247-256. https://doi.org/10.1189/jlb.0504268
Corsini, Emanuela ; Racchi, Marco ; Sinforiani, Elena ; Lucchi, Laura ; Viviani, Barbara ; Rovati, Gian Enrico ; Govoni, Stefano ; Galli, Corrado L. ; Marinovich, Marina. / Age-related decline in RACK-1 expression in human leukocytes is correlated to plasma levels of dehydroepiandrosterone. In: Journal of Leukocyte Biology. 2005 ; Vol. 77, No. 2. pp. 247-256.
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