n-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide and Sinusitis

Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by Th2-skewed inflammation with eosinophilic infiltration. Thymic stromal lymphopoietin (TSLP) promotes the development of allergic inflammation. Although increased TSLP is found in eCRSwNP, little is known about whether TSLP regulates eotaxin-1 production, a potent eosinophil chemoattractant that recruits and activates eosinophils.. The aim of this study was to investigate the effects and mechanisms of TSLP in eotaxin-1 production in the eosinophilic inflammation of eCRSwNP.. Human nasal epithelial cells (HNECs) from eCRSwNP patients were stimulated with recombinant human TSLP in the presence or absence of CYT387 (Janus kinase 1/2 inhibitor). Phosphorylated signal transducer activator of transcription 3 (p-STAT3) was measured by using immunocytochemistry. Eotaxin-1 expression was determined by using real-time PCR. Western blotting was used to detect the levels of p-STAT3 and eotaxin-1 protein.. The treatment with TSLP induced STAT3 phosphorylation in HNECs, and promoted p-STAT3 nuclear translocation, leading to a time-dependent increase of eotaxin-1 expression. However, these effects were attenuated by CYT387 pretreatment.. TSLP regulated eotaxin-1 production in HNECs via JAK1/2-STAT3 signaling, which might contribute to the eosinophilic inflammation of eCRSwNP.

Topics: Adult; Benzamides; Blotting, Western; Chemokine CCL11; Chronic Disease; Cytokines; Eosinophilia; Epithelial Cells; Female; Humans; Immunoenzyme Techniques; Male; Nasal Mucosa; Nasal Polyps; Phosphorylation; Pyrimidines; Real-Time Polymerase Chain Reaction; Rhinitis; Signal Transduction; Sinusitis; STAT3 Transcription Factor; Thymic Stromal Lymphopoietin