STAT6 phosphorylation inhibitors block eotaxin-3 secretion in bronchial epithelial cells
2012
Zhou, Li | Kawate, Tomohiko | Liu, Xiaorong | Kim, Young-Bae | Zhao, Yajuan | Feng, Guohong | Banerji, Julian | Nash, Huw | Whitehurst, Charles | Jindal, Satish | Siddikī, Āraśāda | Seed, Brian | Wolfe, Jia L.
The STAT6 (signal transducer and activator of transcription 6) protein facilitates T-helper cell 2 (Th2) mediated responses that control IgE-mediated atopic diseases such as asthma. We have identified compounds that bind to STAT6 and inhibit STAT6 tyrosine phosphorylation induced by IL-4. In the bronchial epithelial cell line BEAS-2B, compound (R)-84 inhibits the secretion of eotaxin-3, a chemokine eliciting eosinophil infiltration. (R)-84 appears to prevent STAT6 from assuming the active dimer configuration by directly binding the protein and inhibiting tyrosine phosphorylation.
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