Several lines of evidence suggest the importance of low affinity IgE receptor (CD23) in allergic inflammation. A detailed understanding of its intracellular signaling pathways will shed light on mechanisms of allergic diseases and possible therapeutic targets, however these pathways have not been completely elucidated. Two classes of CD23 exist; CD23a, which is expressed constitutively on B cells and CD23b, which is expressed on various cell types including monocytes and macrophages upon induction by multiple cytokines, especially IL-4 and GM-CSF. It has been shown that CD23b is coupled with NF-κB but the proximal signaling events that initiate this signaling cascade are still unknown.

THP-1 cells, a mononuclear leukemic cell line, were stimulated with IL-4 and GM-CSF to up-regulate CD 23 expression confirmed by FACS analysis. Cells were sensitized with IgE, followed by crosslinking with anti-IgE for various time points. then were lysed in 1%NP40 lysis buffer and proteins resolved by SDS-PAGE. Western blot analyses were performed using phosphospecific antibodies to signaling molecules of interest, focusing on signaling molecules upstream of NF-κB.

Within the first 45 minutes after CD23 crosslinking, we found a significant increase in the levels of Src, p38 MAPK, ERK and JNK phosphorylation. We also confirmed IkBa phosphorylation as previously reported.

This is the first report that Src family kinases, p38 MAPK, ERK and JNK are involved in CD23b intracellular signal transduction.