Document Detail

Increased natural killer cell cytotoxicity in Alzheimer's disease may involve protein kinase C dysregulation.
MedLine Citation:
PMID:  9661993     Owner:  NLM     Status:  MEDLINE    
Increased cytokine-mediated cytotoxic natural killer (NK) cell activity has recently been demonstrated in patients with senile dementia of the Alzheimer's type (SDAT). In the present study, we evaluated whether protein-kinase C (PKC), a main regulatory enzyme involved in the mechanism of exocytosis by NK cells, has a role in the cytotoxic response of NK cells (during IL-2 and IFN-beta exposure) from SDAT patients. Our data demonstrate the presence of an increased cytotoxic response by NK cells to IL-2 (mean increase +102%) and IFN-beta (mean increase +132%) in SDAT patients in comparison with healthy elderly subjects (+75% and +88% for IL-2 and IFN-beta, respectively). A smaller suppression of NK cytotoxicity after cortisol was also observed in SDAT (mean decrease -24%) than in the control group (-44%). The NK cell activity of SDAT patients was inversely correlated with the cognitive status as evaluated by the analysis of MMSE (Mini Mental State Examination) score. A comparison of young and elderly healthy subjects revealed no variations in NK cell activity. A physiological decrease in cytosolic PKC activity was demonstrated in healthy old subjects after IL-2 and IFN-beta incubation, but not in SDAT patients, while no variations in kinase activity were observed after cortisol incubation. The decreased activity with cytokines was associated with reduced levels of PKC alpha and betaII isoforms. An alteration in cytokine-mediated NK cell activity associated with PKC dysregulation is therefore suggested to occur in patients with SDAT. These changes may indicate the existence of an immunological component to the pathogenesis and progression of the disease.
S B Solerte; M Fioravanti; A Pascale; E Ferrari; S Govoni; F Battaini
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurobiology of aging     Volume:  19     ISSN:  0197-4580     ISO Abbreviation:  Neurobiol. Aging     Publication Date:    1998 May-Jun
Date Detail:
Created Date:  1998-09-16     Completed Date:  1998-09-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8100437     Medline TA:  Neurobiol Aging     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  191-9     Citation Subset:  IM    
Department of Internal Medicine, Geriatrics and Gerontology Clinic, University of Pavia, Italy.
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MeSH Terms
Alzheimer Disease / enzymology*,  immunology*
Antibody-Dependent Cell Cytotoxicity / physiology*
Blotting, Western
Hydrocortisone / pharmacology
Interferon-beta / pharmacology
Interleukin-2 / pharmacology
Killer Cells, Natural / enzymology*,  immunology*
Leukemia, Myeloid / pathology
Protein Kinase C / metabolism*
Signal Transduction
Tumor Cells, Cultured
Reg. No./Substance:
0/Interleukin-2; 50-23-7/Hydrocortisone; 77238-31-4/Interferon-beta; EC Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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