Document Detail


CXCL9 and CXCL11 chemokines modulation by peroxisome proliferator-activated receptor-alpha agonists secretion in Graves' and normal thyrocytes.
MedLine Citation:
PMID:  20810571     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Peroxisome proliferator-activated receptor (PPAR)-α has been shown to exert immunomodulatory effects in autoimmune disorders. However, until now, no data were present in the literature about the effect of PPARα activation on CXCL9 and CXCL11 chemokines in general or on secretion of these chemokines in thyroid cells.
OBJECTIVE AND DESIGN: The presence of PPARα and PPARγ has been evaluated by real-time-PCR in Graves' disease (GD) and control cells in primary culture. Furthermore, we have tested the role of PPARα and PPARγ activation on CXCL9 and CXCL11 secretion in GD and control cells after stimulation of these chemokines secretion with IFNγ and TNFα.
RESULTS: This study shows the presence of PPARα and PPARγ in GD and control cells. A potent dose-dependent inhibition by PPARα-agonists was observed on the cytokines-stimulated secretion of CXCL9 and CXCL11 in GD and control cells. The potency of the PPARα agonists used was maximum on the secretion of CXCL9, reaching about 90% of inhibition by fenofibrate and 85% by ciprofibrate. The relative potency of the compounds was different with each chemokine; for example, gemfibrozil exerted a 55% inhibition on CXCL11, whereas it had a weaker activity on CXCL9 (40% inhibition). PPARα agonists were stronger (ANOVA, P<0.001) inhibitors of CXCL9 and CXCL11 secretion in thyrocytes than PPARγ agonists.
CONCLUSIONS: Our study shows the presence of PPARα in GD and control thyrocytes. PPARα activators are potent inhibitors of the secretion of CXCL9 and CXCL11, suggesting that PPARα may be involved in the modulation of the immune response in the thyroid.
Authors:
Alessandro Antonelli; Silvia Martina Ferrari; Silvia Frascerra; Cinzia Pupilli; Caterina Mancusi; Maria Rita Metelli; Claudio Orlando; Ele Ferrannini; Poupak Fallahi
Publication Detail:
Type:  Journal Article     Date:  2010-09-01
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-01-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E413-20     Citation Subset:  AIM; IM    
Affiliation:
Department of Internal Medicine, University of Pisa School of Medicine, Via Roma, 67, I-56100, Pisa, Italy. a.antonelli@med.unipi.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Chemokine CXCL11 / drug effects,  secretion*
Chemokine CXCL9 / drug effects,  secretion*
Cytokines / pharmacology
Female
Fenofibrate / pharmacology
Gemfibrozil / pharmacology
Graves Disease / immunology,  physiopathology*,  surgery
Humans
Interferon-gamma / pharmacology
Male
Middle Aged
PPAR alpha / agonists*,  pharmacology,  physiology
PPAR gamma / pharmacology,  physiology
T-Lymphocytes / immunology
Thiazolidinediones / pharmacology
Thyroid Gland / cytology,  drug effects,  pathology
Thyroidectomy
Chemical
Reg. No./Substance:
0/Chemokine CXCL11; 0/Chemokine CXCL9; 0/Cytokines; 0/PPAR alpha; 0/PPAR gamma; 0/Thiazolidinediones; 111025-46-8/pioglitazone; 25812-30-0/Gemfibrozil; 49562-28-9/Fenofibrate; 82115-62-6/Interferon-gamma

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


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