Document Detail


Alternatively activated alveolar macrophages in pulmonary fibrosis-mediator production and intracellular signal transduction.
MedLine Citation:
PMID:  20674506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activated macrophages have been characterized as M1 and M2 according to their inflammatory response pattern. Here we analyzed the M2 marker expression and intracellular signal transduction in the course of cytokine-driven differentiation. We found elevated spontaneous production of the chemokines CCL17, CCL18 and CCL22 and increased expression of CD206 by alveolar macrophages from patients with lung fibrosis. Stimulation of normal human AM with Th2 cytokines IL-4 and/or IL-10 in vitro revealed IL-4 as the most powerful inducer of M2-phenotype in AM and monocytes. Importantly, IL-10 enhanced IL-4-induced expression of CCL18 and IL-1RA in a synergistic fashion. IL-4/IL-10 stimulation induces a strong activation of STAT3 in AM from fibrosis patients. These results suggest an important role for M2 polarized AM in the pathogenesis of pulmonary fibrosis and indicate that both IL-4 and IL-10 account for human AM phenotype shift to M2, as seen in patients with fibrotic interstitial lung diseases.
Authors:
Dmitri V Pechkovsky; Antje Prasse; Florian Kollert; Kathrin M Y Engel; Jan Dentler; Werner Luttmann; Karlheinz Friedrich; Joachim Müller-Quernheim; Gernot Zissel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-31
Journal Detail:
Title:  Clinical immunology (Orlando, Fla.)     Volume:  137     ISSN:  1521-7035     ISO Abbreviation:  Clin. Immunol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-17     Completed Date:  2010-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883537     Medline TA:  Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  89-101     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pneumology, Medical Center, Albert-Ludwigs University, Freiburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Bronchoalveolar Lavage Fluid / cytology
Chemokines, CC / genetics,  metabolism
Cytokines / metabolism*
Female
Gene Expression / drug effects
Humans
Idiopathic Pulmonary Fibrosis / immunology,  metabolism
Interleukin 1 Receptor Antagonist Protein / genetics,  metabolism
Interleukin-10 / pharmacology
Interleukin-4 / pharmacology
Interleukin-8 / metabolism
Lectins, C-Type / metabolism
Macrophage Activation / drug effects,  immunology*
Macrophages, Alveolar / drug effects,  immunology*,  metabolism
Male
Mannose-Binding Lectins / metabolism
Middle Aged
Monocytes / drug effects,  immunology,  metabolism
Pulmonary Fibrosis / etiology,  immunology*,  metabolism
Receptors, Cell Surface / metabolism
STAT Transcription Factors / metabolism
Sarcoidosis, Pulmonary / complications,  diagnosis,  metabolism
Scleroderma, Systemic / complications,  metabolism
Signal Transduction / drug effects,  immunology*
Tumor Necrosis Factor-alpha / metabolism
Young Adult
Chemical
Reg. No./Substance:
0/Chemokines, CC; 0/Cytokines; 0/IL10 protein, human; 0/IL4 protein, human; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-8; 0/Lectins, C-Type; 0/Mannose-Binding Lectins; 0/Receptors, Cell Surface; 0/STAT Transcription Factors; 0/Tumor Necrosis Factor-alpha; 0/mannose receptor; 130068-27-8/Interleukin-10; 207137-56-2/Interleukin-4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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