| IL-4 induces protection of vascular endothelial cells against killing by complement and melittin through lipid biosynthesis. | |
| | |
MedLine Citation:
|
PMID: 20017192 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
We have shown previously that cytokines IL-4 and IL-13 induce protection in porcine vascular endothelial cells (EC) against killing by the membrane attack complex (MAC) of human complement. This protection is intrinsic, not due to changes in complement regulatory proteins, and requires activation of Akt and sterol receptor element binding protein-1 (SREBP-1), which regulates fatty acid and phospholipid synthesis. Here we report that, compared to EC incubated in medium, IL-4-treated EC had a profound reduction in complement-mediated ATP loss and in killing assessed by vital dye uptake, but only a slight reduction in permeability disruption measured by calcein release. While controls exposed to complement lost mitochondrial membrane potential and subsequently died, protected EC maintained mitochondrial morphology and membrane potential, and remained alive. SREBP-1 and fatty acid synthase activation were required for protection and fatty acid and phospholipid synthesis, including cardiolipin, were increased after IL-4 stimulation, without increase in cholesterol content or cell proliferation. IL-4 also induced protection of EC from killing by the channel forming protein melittin, similar to protection observed for the MAC. We conclude that IL-4 induced activation of Akt/SREBP-1/lipid biosynthesis in EC, resulting in protection against MAC and melittin, in association with mitochondrial protection. |
| | |
Authors:
|
Sylvester M Black; Megan E Schott; Bjorn H Batdorf; Barbara A Benson; Mark S Rutherford; Brett K Levay-Young; Agustin P Dalmasso |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
|
Title: European journal of immunology Volume: 40 ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2010 Mar |
Date Detail:
|
Created Date: 2010-03-11 Completed Date: 2010-04-16 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
|
Languages: eng Pagination: 803-12 Citation Subset: IM |
Affiliation:
|
Department of Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blotting, Western Cell Membrane Permeability Cell Separation Complement Membrane Attack Complex / drug effects Complement System Proteins / drug effects* Endothelial Cells / drug effects*, metabolism, ultrastructure Flow Cytometry Interleukin-4 / metabolism, pharmacology* Lipids / biosynthesis* Melitten / adverse effects* Membrane Potential, Mitochondrial / drug effects Microscopy, Electron, Transmission Mitochondria / pathology Proto-Oncogene Proteins c-akt / drug effects, metabolism Signal Transduction / drug effects* Sterol Regulatory Element Binding Protein 1 / drug effects, metabolism Swine |
| Grant Support | |
ID/Acronym/Agency:
|
R01HL062195/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Complement Membrane Attack Complex; 0/Lipids; 0/Sterol Regulatory Element Binding Protein 1; 20449-79-0/Melitten; 207137-56-2/Interleukin-4; 9007-36-7/Complement System Proteins; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: C5a receptor-deficient dendritic cells promote induction of Treg and Th17 cells.
Next Document: Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation.