TY - JOUR T1 - TNFα stimulates the expression different chemokines including CXCl10, CCL5 and CXCL8 in developing airway smooth muscle (ASM) cells: Modulation by fluticasone and TNFα receptors JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - P3713 AU - Hitesh Pandya AU - Abubaccar Gassama AU - Latifa Chachi AU - Helen Pearson AU - Y.S. Prakash AU - Erol Gaillard AU - Yassine Amrani Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/P3713.abstract N2 - Corticosteroids are only partially effective in treating children with Chronic Lung Disease (CLD) or chronic asthma. 'Low to moderate' doses of steroids are generally effective in limiting symptoms, but higher doses are lead to serious side effects with little extra effect on symptom control. In this study, we used fetal ASM cells from human airways to determine their responsiveness to inflammatory chemokines associated with CLD. Fetal ASM cells exposed to TNFα secrete different chemokines including CXCl10, CCL5 and CXCL8. Pre-treating cells with fluticasone (0.001-100nM) led to a dose-dependent suppression of all chemokines although the magnitude of inhibition was greater on CCL5 (over 95%) when compared to CXCl10 or CXCL8 (less than 60%) at 100 nM fluticasone. Using rtPCR, we also found that expression of cytokine genes was only partially repressed by fluticasone (100nm). Neutralizing antibodies against TNFα receptors revealed that engagement of both TNFR1 and TNFR2 mediates TNFα-induced chemokines expression. Our data suggest that generation of pro-inflammatory chemokines by fetal lung cells is only partially responsive to corticosteroid therapy. The mechanisms underlying this resistance are unclear. ER -