Document Detail


Anti-inflammatory cytokine interleukin-19 inhibits smooth muscle cell migration and activation of cytoskeletal regulators of VSMC motility.
MedLine Citation:
PMID:  21209363     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vascular smooth muscle cell (VSMC) migration is an important cellular event in multiple vascular diseases, including atherosclerosis, restenosis, and transplant vasculopathy. Little is known regarding the effects of anti-inflammatory interleukins on VSMC migration. This study tested the hypothesis that an anti-inflammatory Th2 interleukin, interleukin-19 (IL-19), could decrease VSMC motility. IL-19 significantly decreased platelet-derived growth factor (PDGF)-stimulated VSMC chemotaxis in Boyden chambers and migration in scratch wound assays. IL-19 significantly decreased VSMC spreading in response to PDGF. To determine the molecular mechanism(s) for these cellular effects, we examined the effect of IL-19 on activation of proteins that regulate VSMC cytoskeletal dynamics and locomotion. IL-19 decreased PDGF-driven activation of several cytoskeletal regulatory proteins that play an important role in smooth muscle cell motility, including heat shock protein-27 (HSP27), myosin light chain (MLC), and cofilin. IL-19 decreased PDGF activation of the Rac1 and RhoA GTPases, important integrators of migratory signals. IL-19 was unable to inhibit VSMC migration nor was able to inhibit activation of cytoskeletal regulatory proteins in VSMC transduced with a constitutively active Rac1 mutant (RacV14), suggesting that IL-19 inhibits events proximal to Rac1 activation. Together, these data are the first to indicate that IL-19 can have important inhibitory effects on VSMC motility and activation of cytoskeletal regulatory proteins. This has important implications for the use of anti-inflammatory cytokines in the treatment of vascular occlusive disease.
Authors:
Khatuna Gabunia; Surbhi Jain; Ross N England; Michael V Autieri
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-01-05
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  300     ISSN:  1522-1563     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-29     Completed Date:  2011-05-20     Revised Date:  2012-04-02    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C896-906     Citation Subset:  IM    
Affiliation:
Dept. of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Anti-Inflammatory Agents / pharmacology
Cell Movement / drug effects*
Cells, Cultured
Cytoskeletal Proteins / genetics,  metabolism*
Cytoskeleton / drug effects*,  metabolism
HSP27 Heat-Shock Proteins / metabolism
Humans
Interleukins / pharmacology*
Male
Myocytes, Smooth Muscle / cytology,  drug effects*,  physiology*
Phosphorylation
Platelet-Derived Growth Factor / pharmacology
Young Adult
rac1 GTP-Binding Protein / metabolism
rhoA GTP-Binding Protein / metabolism
Grant Support
ID/Acronym/Agency:
HL-090885/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Cytoskeletal Proteins; 0/HSP27 Heat-Shock Proteins; 0/IL19 protein, human; 0/Interleukins; 0/Platelet-Derived Growth Factor; EC 3.6.5.2/rac1 GTP-Binding Protein; EC 3.6.5.2/rhoA GTP-Binding Protein

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