|Inhibition of IL-10 receptor function in alveolar macrophages by Toll-like receptor agonists.|
|PMID: 14764735 Owner: NLM Status: MEDLINE|
|Despite an immunosuppressive lung environment, alveolar macrophages (AM) retain the capacity to respond to microorganisms. This report demonstrates that IL-10, constitutively produced by normal alveolar epithelium, stimulates signal transduction through the IL-10R on AM and that IL-10R function can be inhibited by stimulation of Toll-like receptor (TLR) on AM. IL-10 mRNA and protein were constitutively expressed in normal alveolar epithelium of mice, and IL-10R were constitutively expressed on normal murine AM. Stimulation of AM through TLR2, TLR4, or TLR9 was sufficient to inhibit IL-10R signal transduction, including phosphorylation and nuclear translocation of STAT3 transcription factor. Inhibition of IL-10R function by TLRs was not associated with a decrease in IL-10R expression, but did require expression of the myeloid differentiation factor 88 adaptor protein. Continuous exposure of macrophages to IL-10 caused sustained expression of the chemokine receptors CCR1 and CCR5. However, the addition of TLR ligands inhibited IL-10-induced expression of CCR1 and CCR5. Finally, exposure of macrophages to TLR ligands blocked the ability of IL-10 to inhibit the induction of TNF-alpha by C2-ceramide. These findings demonstrate a novel regulatory mechanism that may allow AM to overcome inhibitory effects of constitutive IL-10 in the lungs that may permit a more effective response to pulmonary infections.|
|Stefan Fernandez; Purnima Jose; Margarita G Avdiushko; Alan M Kaplan; Donald A Cohen|
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|Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.|
|Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 172 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2004 Feb|
|Created Date: 2004-02-06 Completed Date: 2004-06-15 Revised Date: 2007-11-14|
Medline Journal Info:
|Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States|
|Languages: eng Pagination: 2613-20 Citation Subset: AIM; IM|
|Department of Microbiology, University of Kentucky Medical Center, Lexington, KY 40536, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Adaptor Proteins, Signal Transducing
Antigens, Differentiation / genetics, physiology
Bronchoalveolar Lavage Fluid / chemistry, immunology
CpG Islands / immunology
DNA-Binding Proteins / antagonists & inhibitors, metabolism
Dose-Response Relationship, Immunologic
Down-Regulation / genetics, immunology
Immunosuppressive Agents / antagonists & inhibitors, pharmacology
Interleukin-10 / antagonists & inhibitors, metabolism*, pharmacology
Lipopolysaccharides / metabolism, pharmacology
Macrophage Activation / drug effects, immunology
Macrophages, Alveolar / drug effects, immunology*, metabolism*
Membrane Glycoproteins / agonists*, metabolism, physiology*
Mice, Inbred C57BL
Myeloid Differentiation Factor 88
Oligodeoxyribonucleotides / metabolism, pharmacology
Receptors, Cell Surface / agonists*, metabolism, physiology*
Receptors, Immunologic / deficiency, genetics, physiology
Receptors, Interleukin / antagonists & inhibitors*, biosynthesis, physiology*
STAT3 Transcription Factor
Signal Transduction / genetics, immunology
Sphingosine / analogs & derivatives*, antagonists & inhibitors, pharmacology
Teichoic Acids / metabolism, pharmacology
Toll-Like Receptor 2
Toll-Like Receptor 4
Trans-Activators / antagonists & inhibitors, metabolism
|HL57399/HL/NHLBI NIH HHS; HL69459/HL/NHLBI NIH HHS|
|0/Adaptor Proteins, Signal Transducing; 0/Antigens, Differentiation; 0/CPG-oligonucleotide; 0/DNA-Binding Proteins; 0/Immunosuppressive Agents; 0/Ligands; 0/Lipopolysaccharides; 0/Membrane Glycoproteins; 0/Myd88 protein, mouse; 0/Myeloid Differentiation Factor 88; 0/N-acetylsphingosine; 0/Oligodeoxyribonucleotides; 0/Receptors, Cell Surface; 0/Receptors, Immunologic; 0/Receptors, Interleukin; 0/Receptors, Interleukin-10; 0/STAT3 Transcription Factor; 0/Stat3 protein, mouse; 0/Teichoic Acids; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/Toll-Like Receptors; 0/Trans-Activators; 123-78-4/Sphingosine; 130068-27-8/Interleukin-10; 56411-57-5/lipoteichoic acid|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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