Document Detail


Juxtacrine effects of IL-1 alpha precursor promote iNOS expression in vascular smooth muscle cells.
MedLine Citation:
PMID:  11247772     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
After injury to the blood vessel wall, vascular smooth muscle cells (SMC) synthesize interleukin (IL)-1 and inducible nitric oxide (NO) synthase (iNOS). The present study tested whether endogenous production of IL-1 alpha stimulates iNOS expression in vascular SMC, and assessed whether IL-1 alpha exerts autocrine effects on the cells producing IL-1 alpha or juxtacrine effects on cells that contact the IL-1 alpha producing cells. Rat aortic SMC were transiently transfected with expression plasmids encoding either IL-1 alpha precursor, which localizes to the plasma membrane, or mature IL-1 alpha, which remains cytosolic. iNOS mRNA levels, determined by RT-PCR, and production of nitrite, a stable oxidation product of NO, were markedly elevated in SMC overexpressing IL-1 alpha precursor, and modestly elevated in SMC overexpressing mature IL-1 alpha, relative to SMC transfected with vector alone. Exposure to exogenous IL-1 beta or TNF-alpha further stimulated iNOS gene expression in SMC producing IL-1 alpha; low levels of IL-1 beta (20 pg/ml) were effective in SMC transfected with IL-1 alpha precursor plasmid, whereas SMC transfected with mature IL-1 alpha plasmid or vector alone required higher concentrations of IL-1 beta (200 and 2,000 pg/ml, respectively). The increases in iNOS mRNA levels and NO production in SMC overexpressing IL-1 alpha precursor were prevented by exogenous IL-1 receptor antagonist, suggesting that these effects were mediated by the type I IL-1 receptor. Immunostaining studies indicated that IL-1 alpha precursor stimulates iNOS gene expression via cell-cell contact. Expression of iNOS was enhanced in cells that were in contact with a cell overexpressing IL-1 alpha precursor (identified by coexpression of green fluorescent protein), and in cells that were overexpressing IL-1 alpha themselves, but only when the cell contacted another cell. Together these results indicate that IL-1 alpha precursor acts by cell-cell contact as an autocrine and juxtacrine enhancer of iNOS gene expression, inducing moderate iNOS expression on its own, and markedly augmenting the responsiveness of rat aortic SMC to exogenous cytokines.
Authors:
S Sasu; A L Cooper; D Beasley
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  280     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-03-15     Completed Date:  2001-04-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1615-23     Citation Subset:  IM    
Affiliation:
Division of Nephrology, Department of Medicine, New England Medical Center Hospitals and Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic / cytology,  enzymology
Cells, Cultured
Gene Expression Regulation, Enzymologic / drug effects,  physiology*
Interleukin-1 / genetics,  pharmacology,  physiology*
Kinetics
Muscle, Smooth, Vascular / cytology,  enzymology*
Nitric Oxide Synthase / genetics*
Nitric Oxide Synthase Type II
Plasmids
Protein Precursors / genetics
RNA, Messenger / genetics
Rats
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Transcription, Genetic
Transfection
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
ID/Acronym/Agency:
HL-47569/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-1; 0/Protein Precursors; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, rat

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