Antigen-receptor cross-linking and lipopolysaccharide trigger distinct phosphoinositide 3-kinase-dependent pathways to NF-κB activation in primary B cells

被引:39
作者
Bone, H [1 ]
Williams, NA [1 ]
机构
[1] Univ Bristol, Sch Med Sci, Dept Pathol & Microbiol, Bristol BS8 1TD, Avon, England
关键词
BCR; lipopolysaccharide; protein kinase B; protein kinase C;
D O I
10.1093/intimm/13.6.807
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The NF-kappaB/Rel transcription factors play an important role in the expression of genes involved in B cell development, differentiation and function, Nuclear NF-kappaB is induced in B cells by engagement of either the BCR or CD40 or by stimulation with lipopolysaccharide (LPS), Despite the importance of NF-kappaB to a cell function, little is known about the signaling pathways leading to NF-kappaB activation. In this report we address the role of phosphoinositide 3'-kinase (PI 3-kinase) in BCR and LPS-induced NF-kappaB activation using populations of primary murine resting B cells. Using the specific pharmacological inhibitors of PI 3-kinase, Wortmannin and LY294002, we demonstrate that PI 3-kinase activity is vital for BCR-induced NF-kappaB DNA-binding activity. Furthermore, we show that this is achieved via protein kinase C-dependent degradation of I kappaB alpha. Similar analyses reveal that PI 3-kinase is also critical in triggering NF-kappaB DNA-binding activity and I kappaB alpha degradation following LPS stimulation. Interestingly, a PKC inhibitor which blocked the BCR-induced I kappaB alpha degradation had no effect on the degradation of I kappaB alpha after LPS stimulation. Taken together, our results indicate the involvement of PI 3-kinase in at least two distinct signaling pathways leading to activation of NF-kappaB in B cells.
引用
收藏
页码:807 / 816
页数:10
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