| Modulation of chemokines and allergic airway inflammation by selective local sphingosine-1-phosphate receptor 1 agonism in lungs. | |
| | |
MedLine Citation:
|
PMID: 20935081 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Sphingosine-1-phosphate and its receptors have emerged as important modulators of the immune response. The sphingosine-1-phosphate prodrug 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol (FTY720) can alleviate experimental allergic airway inflammation. Nevertheless, the role of individual sphingosine-1-phosphate receptors in the regulation of allergic airway inflammation remains undefined. Using a newly characterized potent and selective sphingosine-1-phosphate receptor 1 (S1P₁) agonist with physical properties allowing airway delivery, we studied the contribution of S1P₁ signaling to eosinophilic airway inflammation induced in ovalbumin-immunized mice by airway challenges with ovalbumin. Airway delivery of receptor-nonselective sphingosine-1-phosphate prodrug significantly inhibits the sequential accumulation of antigen-presenting dendritic cells and CD4+ T cells in draining lymph nodes. This in turn suppressed by >80% the accumulation of CD4+ T cells and eosinophils in the airways. Systemic delivery of sphingosine-1-phosphate prodrug or of an S1P)₁-specific agonist at doses sufficient to induce lymphopenia did not inhibit eosinophil accumulation in the airways. In contrast, local airway delivery of S1P₁-specific agonist inhibited airways release of endogenous CCL5 and CCL17 chemokines, and significantly suppressed accumulation of activated T cells and eosinophils in the lungs. Specific S1P₁ agonism in lungs contributes significantly to anti-inflammatory activities of sphingosine-1-phosphate therapeutics by suppressing chemokine release in the airways, and may be of clinical relevance. |
| | |
Authors:
|
David Marsolais; Saiko Yagi; Tomoyuki Kago; Nora Leaf; Hugh Rosen |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-08 |
Journal Detail:
|
Title: Molecular pharmacology Volume: 79 ISSN: 1521-0111 ISO Abbreviation: Mol. Pharmacol. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2010-12-15 Completed Date: 2011-01-13 Revised Date: 2012-01-02 |
Medline Journal Info:
|
Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: United States |
Other Details:
|
Languages: eng Pagination: 61-8 Citation Subset: IM |
Affiliation:
|
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Allergens
/
toxicity* Animals Chemokines / metabolism*, physiology Lung / drug effects, physiology Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Ovalbumin / toxicity Pneumonia / immunology*, metabolism, pathology* Prodrugs / pharmacology, therapeutic use Receptors, Lysophospholipid / agonists, physiology Receptors, Lysosphingolipid / agonists*, physiology* Thiophenes / pharmacology, therapeutic use beta-Alanine / analogs & derivatives, pharmacology, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
|
AI05509/AI/NIAID NIH HHS; AI074564/AI/NIAID NIH HHS; MH074404/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/AUY 954; 0/Allergens; 0/Chemokines; 0/Prodrugs; 0/Receptors, Lysophospholipid; 0/Receptors, Lysosphingolipid; 0/Thiophenes; 107-95-9/beta-Alanine; 9006-59-1/Ovalbumin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Carotid artery hemodynamics: observing patient-specific changes with amlodipine and lisinopril by us...
Next Document: Aminoglycosides inhibit KCNQ4 channels in cochlear outer hair cells via depletion of phosphatidylino...