Molecular pathways mediating differential responses to lipopolysaccharide between human and baboon arterial endothelial cells

Qiang Shi, Laura A. Cox, Jeremy Glenn, Maria E. Tejero, Vida Hondara, John L. Vandeberg, Xing Li Wang

    Research output: Contribution to journalArticlepeer-review

    18 Scopus citations

    Abstract

    Vascular inflammation plays a critical role in atherogenesis. Previously, we showed that baboon arterial endothelial cells (BAEC) were hyporesponsive to lipopolysaccharide (LPS) compared with human arterial endothelial cells (HAEC). 2. In the present study, we investigated mechanisms underlying differential responses between HAEC and BAEC to tumour necrosis factor (TNF)-α and LPS. 3. Both HAEC and BAEC responded similarly to TNF-α. However, BAEC showed retarded responses to LPS in expression of E-selectin, intercellular adhesion molecule-1, monocyte chemotactic protein-1 and interleukin-8 (P < 0.05). These changes were confirmed at the mRNA level. Tumour necrosis factor-α activated nuclear factor-κB members such as p50, p52, p65, c-rel and RelB in both HAEC and BAEC. In contrast, LPS activated p50 and p65 only in HAEC. Using microarray assays, we found that TNF receptor-associated factor 2 (TRAF-2), TNF receptor superfamily, member 1A-associated via death domain (TRADD) and nuclear factors such as nuclear factor of kappa in B-cells inhibitor, α (NFKBIA) and nuclear factor of kappa in B-cells inhibitor, β (NFKBIB) were upregulated by LPS only in HAEC. Although the baseline expression of Toll-like receptor (TLR) 4 was low in both HAEC and BAEC, TNF-α activated TLR4 expression in both cell types. Although LPS increased TLR4 expression only in HAEC, human and baboon peripheral blood mononuclear cells exhibited similar TLR4 expression and response to LPS. Transfecting BAEC with TLR4/myeloid differentiation protein-2 overexpression vector conferred BAEC responsiveness to LPS. 4. The findings of the present study indicate that an altered TLR4 system may be responsible for the resistance of baboon endothelial cells to LPS. Given the importance of TLR4 in human immune responses and vascular diseases, the natural resistance of baboons to LPS/TLR4-initiated inflammation could make the baboon a valuable animal model in which to study how inflammation affects atherogenesis.

    Original languageEnglish (US)
    Pages (from-to)178-184
    Number of pages7
    JournalClinical and Experimental Pharmacology and Physiology
    Volume37
    Issue number2
    DOIs
    StatePublished - Feb 2010

    Keywords

    • Baboons
    • Endothelial cells
    • Inflammatory reactions
    • Lipopolysaccharide
    • Toll-like receptor 4

    ASJC Scopus subject areas

    • Physiology
    • Pharmacology
    • Physiology (medical)

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