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aa155-171 motif deletion of MyD88 attenuates expression of co-stimulatory molecules and cytokines in immune associated-cells |
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Abstract Myeloid differentiation factor MyD88 is a critical adaptor molecule that integrates and transduces intracellular signals in inducing the differentiation of dendritic cells (DCs). We searched the domain regions within MyD88 which could potentially affect the function of dendritic cells and found that MyD88 aa155-171 motif not only regulate the activity of transcription factor NF-κB but also control the production of cytokines and expression of costimulatory molecules. Indeed, aa155-171 motif deleted type MyD88 (MyD88?155-171) transfected RAW264.7 exhibited the reduced NF-內B and AP-1 activity and interrupted the expression of CD86 and B7H1. Meanwhile, lower level expression of cytokines such as IL-12,IFN-r were observed by means of cytokine array techniques in MyD88-/- DC trasfected with MyD88?155-171 as compared to the MyD88 transfected cells. Thus, aa155-171 motif inside MyD88 could affect the expression of costimulatory molecules, cytokines secretion and interrupt Toll like receptor signal pathway, suggesting that this motif may play an important role in regulating responses of innate immune system.
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Received: 24 March 2008
Published: 25 September 2008
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