Aggregation of the high-affinity IgE receptor FcεRI on human monocytes and dendritic cells induces NF-κB activation

被引:52
|
作者
Kraft, S
Novak, N
Katoh, N
Bieber, T
Rupec, RA
机构
[1] Univ Bonn, Dept Dermatol, D-53105 Bonn, Germany
[2] Kyoto Prefectural Univ, Dept Dermatol, Kyoto 606, Japan
[3] Univ Munich, Dept Dermatol & Allergy, Munich, Germany
关键词
atopy; dendritic cells; IgE receptor; inflammation; NF-kappa B;
D O I
10.1046/j.1523-1747.2002.01757.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
In contrast to mast cells and basophils, the high-affinity IgE receptor (FcepsilonRI) on monocytes and dendritic cells (DC), including epidermal Langerhans cells, is not constitutively expressed and lacks the beta-chain. FcepsilonRI is upregulated on Langerhans cells of atopic individuals, particularly in atopic dermatitis skin. Although FcepsilonRI provides IgE-mediated antigen focusing on monocytes and DC/Langerhans cells, its relevance for cell activation remains elusive, and the transcription factors regulating FcepsilonRI-induced genes are unknown. We show that NF-kappaB, known to regulate genes essential for inflammatory responses and DC differentiation and function, is activated upon FcepsilonRI ligation in primary human monocytes and DC. In Langerhans cells isolated from epidermis, NF-kappaB activation is restricted to donors expressing high FcepsilonRI amounts. FcepsilonRI-induced NF-kappaB complexes in monocytes and DC contain p50 and p65, but no other NF-kappaB subunits despite increased RelB expression during differentiation. NF-kappaB activation is preceded by serine phosphorylation and degradation of its inhibitory protein IkappaB-alpha without involving other IkappaB proteins. Finally, we show that FcepsilonRI ligation on monocytes and DC leads to synthesis and release of tumor necrosis factor-alpha and monocyte chemoattractant protein-1, which is decreased by two mechanistically distinct inhibitors of NF-kappaB activation. Thus NF-kappaB activation represents a novel mechanism by which FcepsilonRI on monocytes and DC potentially controls inflammatory reactions.
引用
收藏
页码:830 / 837
页数:8
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