TY - JOUR T1 - Inhibition of JAK/STAT pathway in airway epithelium as a potential targeted therapy of asthma JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - 3413 AU - Anna Bujak AU - Patrycja Nejman-Gryz AU - Pawel Gunerka AU - Monika Lamparska-Przybysz AU - Maciej Wieczorek AU - Ryszarda Chazan AU - Aleksandra Stanczak Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/3413.abstract N2 - INTRODUCTIONEpithelial cells play an important role in immune response and eosinophilic airway inflammation, contributing to the pathogenesis of asthma. JAK/STAT pathway is involved in transduction of signal from cytokines' receptors and expression of downstream cytokines and chemokines. Therefore, inhibition of JAKs seems to be a promising approach for the therapy of asthma.MATHERIALS AND METHODSJAKs inhibitors: baricitinib, tofacitinib and gandotinib were used to study a role of JAK/STAT pathway in airway epithelium. Their activity among the JAKs kinases was assessed by ATP-based enzymatic assay. Their biological potency was evaluated in Primary Bronchial Tracheal Epithelial Cells (PBTEC) by WB and ELISA.RESULTSBaricitinib has a great potency to inhibit JAK1/JAK2, tofacitinib inhibits JAK2/JAK3, while gandotinib is a potent JAK2 inhibitor.View this table:Table 1. Selectivity of JAKs inhibitorWe showed significant inhibition of STAT6 phosphorylation in cytokines' stimulated PBTEC after treatment with tofacitinib and baricitinib at concentration of 0,5μM, and gandotinib at 1μM. We showed corresponding decrease of eotaxin-3 secretion by cells treated with tofacitinib (IC50<10nM), baricitinib (10nM<IC50<100nM) and gandotinib (100nM<IC50<1000nM).CONCLUSIONIn airway epithelium model we observed distinct effect on eotaxin-3 release of JAKs inhibitors with higher activity towards JAK3 (tofacitinib) and JAK1 (baricitinib) from that of gandonitinib, the selective JAK2 inhibitor. Our results confirm that targeting JAK/STAT pathway represents a promising strategy for the therapy of asthma. ER -