Document Detail


Modulation of the development of human monocyte-derived dendritic cells by lithium chloride.
MedLine Citation:
PMID:  20672290     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lithium has been used or explored to treat psychiatric and neurodegenerative diseases that are frequently associated with an abnormal immune status. It is likely that lithium may work through modulation of immune responses in these patients. Because dendritic cells (DC) play a central role in regulating immune responses, this study investigated the influence of lithium chloride (LiCl) on the development and function of DC. Exposure to LiCl during the differentiation of human monocyte-derived immature DCs (iDC) enhances CD86 and CD83 expression and increases the production of IL-1β, IL-6, IL-8, IL-10, and TNF-α. However, the presence of LiCl during LPS-induced maturation of iDC has the opposite effect. During iDC differentiation, LiCl suppresses the activity of glycogen synthase kinase (GSK)-3β, and activates PI3K and MEK. In addition, LiCl activates peroxisome proliferator-activated receptor γ (PPARγ) during iDC differentiation, a pathway not described before. Each of these signaling pathways appears to have distinct impact on the differentiating iDC. The enhanced CD86 expression by LiCl involves the PI3K/AKT and GSK-3β pathway. LiCl modulates the expression of CD83 in iDC mainly through MEK/ERK, PI3K/AKT, and PPARγ pathways, while the increased production of IL-1β and TNF-α mainly involves the MEK/ERK pathway. The effect of LiCl on IL-6/IL-8/IL-10 secretion in iDC is mediated through inhibition of GSK-3β. We have also demonstrated that PPARγ is downstream of GSK-3β and is responsible for the LiCl-mediated modulation of CD86/83 and CD1 expression, but not IL-6/8/10 secretion. The combined influence of these molecular signaling pathways may account for certain clinical effect of lithium.
Authors:
Ko-Jiunn Liu; Yueh-Lun Lee; Yi-Yuan Yang; Neng-Yao Shih; Chia-Chen Ho; Yu-Chen Wu; Tze-Sing Huang; Ming-Chyi Huang; Hsing-Cheng Liu; Winston W Shen; Sy-Jye Leu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  226     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2011-01-06     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  424-33     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc.
Affiliation:
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Adjuvants, Immunologic / pharmacology
Animals
Antigens, CD / immunology
Antigens, CD86 / immunology
Cell Differentiation / drug effects,  immunology
Cells, Cultured
Dendritic Cells / cytology,  drug effects*,  physiology*
Enzyme Inhibitors / metabolism
Glycogen Synthase Kinase 3 / immunology
Humans
Immunoglobulins / immunology
Interleukins / immunology
Lithium Chloride / pharmacology*
Membrane Glycoproteins / immunology
Mitogen-Activated Protein Kinase Kinases / immunology
Monocytes / cytology,  drug effects*,  physiology*
PPAR gamma / immunology
Phosphatidylinositol 3-Kinases / metabolism
Signal Transduction
Tumor Necrosis Factor-alpha / immunology
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Antigens, CD; 0/Antigens, CD86; 0/CD83 antigen; 0/Enzyme Inhibitors; 0/Immunoglobulins; 0/Interleukins; 0/Membrane Glycoproteins; 0/PPAR gamma; 0/Tumor Necrosis Factor-alpha; 7447-41-8/Lithium Chloride; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases

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


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