| Toll-like receptor (TLR)-9 genetics and function in sarcoidosis. | |
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MedLine Citation:
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PMID: 20659127 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sarcoidosis is a systemic disorder characterized by the formation of non-caseating granulomas in variable organs. Toll-like receptor (TLR)-9 is important in the innate immune response against both Mycobacterium tuberculosis and Propionibacterium acnes, candidate causative agents in sarcoidosis. The aim of our study was to investigate possible genetic and functional differences in TLR-9 between patients and controls. TLR-9 single nucleotide polymorphisms were genotyped in 533 patients and divided into a study cohort and validation cohort and 185 healthy controls. Furthermore, part of the promotor as well as the entire coding region of the TLR-9 gene were sequenced in 20 patients in order to detect new mutations. No genetic differences were found between patients and controls. In order to test TLR-9 function, peripheral blood mononuclear cells (PBMCs) of 12 healthy controls and 12 sarcoidosis patients were stimulated with a TLR-9 agonist and the induction of interleukin (IL)-6, interferon (IFN)-γ and IL-23 was measured. Sarcoidosis patients produce significantly less IFN-γ upon stimulation with different stimuli. Regarding IL-23 production, a significant difference between patients and controls was found only after stimulation with the TLR-9 agonist. In conclusion, we did not find genetic differences in the TLR-9 gene between sarcoidosis patients and controls. Sarcoidosis patients produce less IFN-γ regardless of the stimulating agent, probably reflecting the anergic state often seen in their peripheral blood T lymphocytes. The differences in TLR-9-induced IL-23 production could indicate that functional defects in the TLR-9 pathway of sarcoidosis patients play a role in disease susceptibility or evolution. |
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Authors:
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M Veltkamp; C H M Van Moorsel; G T Rijkers; H J T Ruven; J M M Van Den Bosch; J C Grutters |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-19 |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 162 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-13 Completed Date: 2010-10-29 Revised Date: 2012-05-07 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 68-74 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology. |
Affiliation:
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Center for Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital, Nieuwegein Division of Heart and Lungs, University Medical Center, Utrecht, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cells, Cultured Cohort Studies DNA Mutational Analysis Enzyme-Linked Immunosorbent Assay Female Gene Frequency Genotype Humans Interferon-gamma / metabolism Interleukin-23 / metabolism Interleukin-6 / metabolism Leukocytes, Mononuclear / cytology, drug effects, metabolism Linkage Disequilibrium Male Oligonucleotides / pharmacology Phytohemagglutinins / pharmacology Polymorphism, Single Nucleotide* Promoter Regions, Genetic / genetics* Sarcoidosis / genetics*, pathology Toll-Like Receptor 9 / agonists, genetics*, physiology |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-23; 0/Interleukin-6; 0/Oligonucleotides; 0/Phytohemagglutinins; 0/TLR9 protein, human; 0/Toll-Like Receptor 9; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
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