Association between CD14 polymorphisms and serum soluble CD14 levels: effect of atopy and endotoxin inhalation.

T.D. Levan, O. Michel, M. Dentener, J. Thorn, F. Vertongen, L. Beijer, F.D. Martinez

    Research output: Contribution to journalArticleAcademicpeer-review

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    Abstract

    BACKGROUND: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. OBJECTIVE: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. METHODS: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 mug of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. RESULTS: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. CONCLUSION: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels. CLINICAL IMPLICATIONS: This might represent a mechanism by which CD14 polymorphisms and endotoxin exposure differentially result in disease status.
    Original languageEnglish
    Pages (from-to)434-440
    JournalJournal of Allergy and Clinical Immunology
    Volume121
    Issue number2
    DOIs
    Publication statusPublished - 1 Jan 2008

    Cite this

    Levan, T.D. ; Michel, O. ; Dentener, M. ; Thorn, J. ; Vertongen, F. ; Beijer, L. ; Martinez, F.D. / Association between CD14 polymorphisms and serum soluble CD14 levels: effect of atopy and endotoxin inhalation. In: Journal of Allergy and Clinical Immunology. 2008 ; Vol. 121, No. 2. pp. 434-440.
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    abstract = "BACKGROUND: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. OBJECTIVE: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. METHODS: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 mug of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. RESULTS: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. CONCLUSION: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels. CLINICAL IMPLICATIONS: This might represent a mechanism by which CD14 polymorphisms and endotoxin exposure differentially result in disease status.",
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    Association between CD14 polymorphisms and serum soluble CD14 levels: effect of atopy and endotoxin inhalation. / Levan, T.D.; Michel, O.; Dentener, M.; Thorn, J.; Vertongen, F.; Beijer, L.; Martinez, F.D.

    In: Journal of Allergy and Clinical Immunology, Vol. 121, No. 2, 01.01.2008, p. 434-440.

    Research output: Contribution to journalArticleAcademicpeer-review

    TY - JOUR

    T1 - Association between CD14 polymorphisms and serum soluble CD14 levels: effect of atopy and endotoxin inhalation.

    AU - Levan, T.D.

    AU - Michel, O.

    AU - Dentener, M.

    AU - Thorn, J.

    AU - Vertongen, F.

    AU - Beijer, L.

    AU - Martinez, F.D.

    PY - 2008/1/1

    Y1 - 2008/1/1

    N2 - BACKGROUND: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. OBJECTIVE: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. METHODS: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 mug of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. RESULTS: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. CONCLUSION: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels. CLINICAL IMPLICATIONS: This might represent a mechanism by which CD14 polymorphisms and endotoxin exposure differentially result in disease status.

    AB - BACKGROUND: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. OBJECTIVE: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. METHODS: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 mug of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. RESULTS: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. CONCLUSION: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels. CLINICAL IMPLICATIONS: This might represent a mechanism by which CD14 polymorphisms and endotoxin exposure differentially result in disease status.

    U2 - 10.1016/j.jaci.2007.08.050

    DO - 10.1016/j.jaci.2007.08.050

    M3 - Article

    VL - 121

    SP - 434

    EP - 440

    JO - Journal of Allergy and Clinical Immunology

    JF - Journal of Allergy and Clinical Immunology

    SN - 0091-6749

    IS - 2

    ER -