期刊
JOURNAL OF IMMUNOLOGY
卷 175, 期 4, 页码 2082-2090出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.4.2082
关键词
-
类别
资金
- NIAID NIH HHS [5R01AI056484] Funding Source: Medline
Activation of APCs via TLRs leads to activation of NF-kappa B, a key transcription factor in cells of the immune system most often associated with induction of Th1-type and proinflammatory responses. The neoglycoconjugate lacto-N-fucopentaose III (12-25 molecules)-dextran (LNFPIII-Dex) activates dendritic cells (DCs) via TLR4, as does LPS. However, unlike LPS, LNFPIII-Dex-activated cells induce Th2-type CD4(+) T c ell responses. This observation led us to ask whether LNFPIII-activated APCs were differentially activating NF-kappa B and if so, could this partly account for how DCs mature in response to these two different pathogen-associated molecular patterns (PAMPs). In this study, we show that LNFPIII-Dex stimulation of APCs induces rapid, but transient NF-kappa B translocation and activity in the nucleus, in comparison with the persistent activation induced by LPS. We then demonstrate that transient vs persistent NF-kappa B activation has important implications in the development of the APC phenotype, showing that the second wave of NF-kappa B translocation in response to LPS is required for production of the proinflammatory mediator NO. In contrast to LPS, LNFPIII-stimulated APCs that only transiently activate NF-kappa B do not induce degradation of the known I kappa B family members or production of NO. However, cells stimulated with LNFPIII rapidly accumulate p50, suggesting that an alternative p105 degradation-dependent mechanism is primarily responsible for NF-kappa B activation downstream of LNFPIII. Finally, we show that while NF-kappa B translocation in LNFPIII-stimulated APCs is transient, it is required for the development of the DC 2 phenotype, confirming a crucial and multifaceted role for NF-kappa B in innate immune responses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据