A promoter polymorphism in the CD14 gene is associated with elevated levels of soluble CD14 but not with IgE or atopic diseases

Kabesch, Michael; Hasemann, K.; Schickinger, V.; Tzotcheva, Iren; Bohnert, Anette; Carr, David; Baldini, Mauro; Hackstein, Holger; Leupold, W; Weiland, Stephan K.; Martínez, Fernando D.; Mutius, Erika von; Bein, Gregor

doi:10.1111/j.1398-9995.2004.00439.x

Cited by 88 publications

(90 citation statements)

References 25 publications

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“…Similar results have been observed in adolescent and adult subjects for CD14/À1720 12 and CD14/À260. 4,[12][13][14] No association was found between CD14/À2838 and post-natal sCD14 levels. Haplotype analysis did not show any effect stronger than individual genotype data (data not shown).…”

Section: Resultsmentioning

confidence: 64%

The impact of CD14 polymorphisms on the development of soluble CD14 levels during infancy

et al. 2006

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CD14 is a receptor involved in the recognition of lipopolysaccharide and other bacterial wall components that may be involved in the balance between infectious and allergic disease and the early polarization towards TH1. Our group has shown an association between polymorphisms in the 5 0 flanking region of the CD14 gene and plasma soluble CD14 (sCD14) levels at 11 years of age. However, whether this association is present at birth and in infancy remains to be determined. In this study, we measured sCD14 levels in plasma from the umbilical cord (n ¼ 387) and at 3 months (n ¼ 357) and 1 year (n ¼ 312) of age in non-selected healthy infants to assess their relationship with CD14 genotypes at À4190, À2838, À1720 and À260 (relative to translation start site). There was no relation of CD14 genotypes with sCD14 at birth. However, there was a significant association between CD14 genotypes and sCD14 as early as 3 months. Longitudinal analysis suggests that CD14 polymorphisms modulate sCD14 levels up to 1 year of age. This association early in life may have an impact on TH1 polarization and subsequent protection against allergic disease.

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Section: Resultsmentioning

confidence: 64%

The impact of CD14 polymorphisms on the development of soluble CD14 levels during infancy

et al. 2006

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“…[13][14][15] Likewise, asthma has in some studies been associated with polymorphisms in TLR2, 16 TLR4 17 and CD14, 18 but not in others. [19][20][21] Epidemiological studies suggest a negative relation between asthma and T1D 22 and certain genes appear to have associations in opposite directions for these two diseases. 23 To our knowledge, polymorphisms in these PRRs have not been compared in relation to T1D and allergic asthma, and the recent observation that PRRs are involved in regulation of Th1 versus Th2 responses raises the question of common genetic variants in these diseases.…”

Section: Introductionmentioning

confidence: 99%

A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma

et al. 2009

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Type 1 diabetes (T1D) and allergic asthma are immune-mediated diseases. Pattern recognition receptors are proteins expressed by cells in the immune system to identify microbial pathogens and endogenous ligands. Toll-like receptors (TLRs) and CD14 are members of this family and could represent a molecular link between microbial infections and immune-mediated diseases. Diverging hypotheses regarding whether there exists a common or inverse genetic etiology behind these immunemediated diseases have been presented. We aimed to test whether there exist common or inverse associations between polymorphisms in the pattern recognition receptors TLR2, TLR4 and CD14 and T1D and allergic asthma. Eighteen single nucleotide polymorphisms (SNPs) were genotyped in TLR2 (2), TLR4 (12) and CD14 (4) in 700 T1D children, 357 nuclear families with T1D children and 796 children from the 'Environment and Childhood Asthma' study. Allele and haplotype frequencies were analyzed in relation to diseases and in addition transmission disequilibrium test analyses were performed in the family material. Both T1D and allergic asthma were significantly associated with the TLR2 rs3804100 T allele and further associated with the haplotype including this SNP, possibly representing a susceptibility locus common for the two diseases. Neither TLR4 nor CD14 were associated with T1D or allergic asthma.

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“…Recently, a single-nucleotide polymorphism in the promoter region of CD14 has been studied in patients with allergy [26][27][28][29][30][31]. Early studies suggested that this variant, which affects the soluble CD14 level [27,28], was associated with more severe atopy [27,29,30].…”

Section: Discussionmentioning

confidence: 99%

Trans-Basement Membrane Migration of Eosinophils Induced By LPS-Stimulated Neutrophils from Human Peripheral Blood in Vitro

Nakagome

Nishihara

Kobayashi

et al. 2016

Journal of Allergy and Clinical Immunology

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In the airways of severe asthmatics, an increase of neutrophils and eosinophils is often observed despite high-dose corticosteroid therapy. We previously reported that interleukin-8-stimulated neutrophils induced trans-basement membrane migration (TBM) of eosinophils, suggesting the link between neutrophils and eosinophils. Concentrations of lipopolysaccharide (LPS) in the airway increase in severe asthma. As neutrophils express Toll-like receptor (TLR)4 and can release chemoattractants for eosinophils, we investigated whether LPS-stimulated neutrophils modify eosinophil TBM.Neutrophils and eosinophils were isolated from peripheral blood of healthy volunteers and severe asthmatics. Eosinophil TBM was examined using a modified Boyden's chamber technique. Eosinophils were added to the upper compartment, and neutrophils and LPS were added to the lower compartment. Migrated eosinophils were measured by eosinophil peroxidase assays.LPS-stimulated neutrophils induced eosinophil TBM (about 10-fold increase), although LPS or neutrophils alone did not. A leukotriene B 4 receptor antagonist, a platelet-activating factor receptor antagonist or an anti-TLR4 antibody decreased eosinophil TBM enhanced by LPS-stimulated neutrophils by almost half. Neutrophils from severe asthmatics induced eosinophil TBM and lower concentrations of LPS augmented neutrophil-induced eosinophil TBM.These results suggest that the combination of neutrophils and LPS leads eosinophils to accumulate in the airways, possibly involved the pathogenesis of severe asthma. @ERSpublications LPS-stimulated neutrophils induced eosinophil TBM, which may be involved in the pathogenesis of severe asthma

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A promoter polymorphism in the CD14 gene is associated with elevated levels of soluble CD14 but not with IgE or atopic diseases

Abstract: The lack of association between CD14 genotypes and IgE as well as atopic outcomes in this large German study population seems to indicate that CD14 genotypes may not directly be involved in the development of allergies during childhood.

Cited by 88 publications

References 25 publications

The impact of CD14 polymorphisms on the development of soluble CD14 levels during infancy

The impact of CD14 polymorphisms on the development of soluble CD14 levels during infancy

A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma

Trans-Basement Membrane Migration of Eosinophils Induced By LPS-Stimulated Neutrophils from Human Peripheral Blood in Vitro

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