Document Detail

Resveratrol inhibits high glucose-induced PI3K/Akt/ERK-dependent interleukin-17 expression in primary mouse cardiac fibroblasts.
MedLine Citation:
PMID:  18310510     Owner:  NLM     Status:  MEDLINE    
We investigated the expression of the proinflammatory cytokine interleukin (IL)-17 in cardiac fibroblasts and its induction by high glucose (HG). Our results show that primary mouse cardiac fibroblasts (mCFs) secrete low basal levels of IL-17 and that HG (25 mM D-glucose) as opposed to low glucose (5 mM D-glucose + 20 mM mannitol) significantly enhances its secretion. HG induces IL-17 mRNA expression by both transcriptional and posttranscriptional mechanisms. HG induces phosphoinositide 3- kinase [PI3K; inhibited by adenoviral (Ad).dominant negative (dn)PI3Kp85], Akt (inhibited by Ad.dnAkt1), and ERK (inhibited by PD-98059) activation and induces IL-17 expression via PI3K-->Akt-->ERK-dependent signaling. Moreover, mCFs express both IL-17 receptors A and C, and although IL-17RA is upregulated, HG fails to modulate IL-17RC expression. Furthermore, IL-17 stimulates net collagen production by mCFs. Pretreatment with the phytoalexin resveratrol blocks HG-induced PI3K-, Akt-, and ERK-dependent IL-17 expression. These results demonstrate that 1) cardiac fibroblasts express IL-17 and its receptors; 2) HG upregulates IL-17 and IL-17RA, suggesting a positive amplification loop in IL-17 signaling in hyperglycemia; 3) IL-17 enhances net collagen production; and 4) resveratrol can inhibit these HG-induced changes. Thus, in hyperglycemic conditions, IL-17 may potentiate myocardial inflammation, injury, and remodeling through autocrine and paracrine mechanisms, and resveratrol has therapeutic potential in ameliorating this effect.
Kaliyamurthi Venkatachalam; Srinivas Mummidi; Dolores M Cortez; Sumanth D Prabhu; Anthony J Valente; Bysani Chandrasekar
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-02-29
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  294     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-07     Completed Date:  2008-06-12     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2078-87     Citation Subset:  IM    
Department of Veterans' Affairs, South Texas Veterans Health Care System-Audie L. Murphy Division, San Antonio, TX 78229-3900, USA.
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MeSH Terms
Cardiovascular Agents / pharmacology*
Cell Culture Techniques
Cells, Cultured
Collagen / metabolism
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  metabolism*
Fibroblasts / drug effects*,  enzymology,  metabolism
Flavonoids / pharmacology
Glucose / metabolism*
Hyperglycemia / enzymology,  metabolism
Interleukin-17 / genetics,  metabolism*
Mice, Inbred C57BL
Myocardium / enzymology,  metabolism*
Phosphatidylinositol 3-Kinases / genetics,  metabolism*
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-akt / genetics,  metabolism*
RNA, Messenger / metabolism
Receptors, Interleukin / metabolism
Receptors, Interleukin-17 / metabolism
Signal Transduction / drug effects
Stilbenes / pharmacology*
Time Factors
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Cardiovascular Agents; 0/Flavonoids; 0/Il17r protein, mouse; 0/Il17rc protein, mouse; 0/Interleukin-17; 0/Protein Kinase Inhibitors; 0/RNA, Messenger; 0/Receptors, Interleukin; 0/Receptors, Interleukin-17; 0/Stilbenes; 50-99-7/Glucose; 9007-34-5/Collagen; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Proteins c-akt; EC Signal-Regulated MAP Kinases; Q369O8926L/resveratrol

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