Document Detail


CD14, a key candidate gene associated with a specific immune response to cockroach.
MedLine Citation:
PMID:  20618347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Sensitization to cockroach allergen is one of the strongest predictors of asthma morbidity, especially among African Americans.
OBJECTIVE: Our aims were to determine the genomic basis of cockroach sensitization and the specific response to cockroach antigen.
METHODS: We investigated the Th1/Th2 cytokine profile of co-cultured plasmacytoid dendritic cells (pDCs) and CD4+ T cells and the 'transcript signature' of the immune response to cockroach antigen using high-throughput expression profiling of co-cultured cells.
RESULTS: We observed significantly elevated levels of IL-13, IL-10, and TNF-alpha, but undetectable levels of IL-12p70 and IFN-alpha, when cultures were exposed to crude cockroach antigen. A significant difference was observed for IL-13 between cockroach-allergic and non-allergic individuals (P=0.039). Microarray analyses demonstrated a greater response at 48 h compared with 4 h, with 50 genes being uniquely expressed in cockroach antigen-treated cells, including CD14, S100A8, CCL8, and IFI44L. The increased CD14 expression was further observed in purified pDCs, human monocytic THP-1 cells, and the supernatant of co-cultured pDCs and CD4+ T cells on exposure to cockroach extract. Furthermore, the most differential expression of CD14 between cockroach allergy and non-cockroach allergy was only observed among individuals with the CC 'high-risk' genotype of the CD14-260C/T. Ingenuity Pathways Analysis analyses suggested the IFN signalling as the most significant canonical pathway.
CONCLUSION: Our results suggest that these differentially expressed genes, particularly CD14, and genes in the IFN signalling pathway may be important candidates for further investigation of their role in the immune response to cockroach allergen.
Authors:
P Gao; D N Grigoryev; N M Rafaels; D Mu; J M Wright; C Cheadle; A Togias; T H Beaty; R A Mathias; J T Schroeder; K C Barnes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-04
Journal Detail:
Title:  Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology     Volume:  40     ISSN:  1365-2222     ISO Abbreviation:  Clin. Exp. Allergy     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-12     Completed Date:  2011-01-25     Revised Date:  2011-09-13    
Medline Journal Info:
Nlm Unique ID:  8906443     Medline TA:  Clin Exp Allergy     Country:  England    
Other Details:
Languages:  eng     Pagination:  1353-64     Citation Subset:  IM    
Affiliation:
Department of Medicine, Division of Allergy and Clinical Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
African Americans
Allergens / immunology*
Animals
Antigens, CD14 / genetics*
Asthma / ethnology,  genetics*,  immunology
CD4-Positive T-Lymphocytes / immunology,  metabolism
Cockroaches / immunology*
Coculture Techniques
Cytokines / biosynthesis*
Dendritic Cells / immunology,  metabolism
Gene Expression Profiling*
Genetic Predisposition to Disease*
Genotype
Humans
Interferon-alpha / immunology*,  metabolism
Middle Aged
Th2 Cells
Grant Support
ID/Acronym/Agency:
AI50024/AI/NIAID NIH HHS; HL087699/HL/NHLBI NIH HHS; HL72455/HL/NHLBI NIH HHS; R01 AI050024-01A2/AI/NIAID NIH HHS; R01 HL087699-01/HL/NHLBI NIH HHS; R21 AI088406-02/AI/NIAID NIH HHS; U01 HL072455-01/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Allergens; 0/Antigens, CD14; 0/Cytokines; 0/Interferon-alpha
Comments/Corrections

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