期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 85, 期 4, 页码 648-655出版社
WILEY
DOI: 10.1189/jlb.0708428
关键词
human; bacterial infection; inflammation; gene regulation; molecular biology
资金
- American Diabetes Association
- Evans Medical Foundation
- USPHS [DE15566]
- [R01 AI54611]
Chronic systemic inflammation links periodontal disease (PD) to increased incidence of cardiovascular disease. Activation of TLRs, particularly TLR4, promotes chronic inflammation in PD by stimulating myeloid cells. B cells from healthy individuals are generally refractory to TLR4 agonists as a result of low surface TLR4 expression. Unexpectedly, a significantly increased percentage of gingival and peripheral blood B cells from patients with PD expressed surface TLR4. Surface expression correlated with an active TLR4 promoter that mimicked the TLR4 promoter in neutrophils. B cells from PD patients were surface myeloid differentiation protein 2-positive and also packaged the enhancer of a proinflammatory cytokine, IL-1 beta, into an active structure, demonstrating that these cells harbor key characteristics of proinflammatory cell types. Furthermore, B cells lacked activating signatures of a natural IL-1 beta inhibitor, IL-1 receptor antagonist. Surprisingly, despite multiple signatures of proinflammatory cells, freshly isolated B cells from PD patients had decreased expression of TLR pathway genes compared with B cells from healthy individuals. Decreases in inflammatory gene expression were even more dramatic in B cells stimulated with a TLR4 ligand from a periodontal pathogen, Porphyromonas gingivalis LPS 1690. In contrast, B cell TLR4 was not activated by the prototypic TLR4 ligand Escherichia coli LPS. These findings raise the unexpected possibility that TLR4 engagement modulates B cell activation in PD patients. J. Leukoc. Biol. 85: 648-655; 2009.
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