TY - JOUR T1 - LSC 2011 Abstract: Inflammation and COPD: Protective effect of the recombinant anti-protease trappin-2 A62L, on lung epithelium JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p415 AU - Annabelle Tanga AU - Alhame Saidi AU - Sandrine Dallet-Choisy AU - Marie-Louise Zani AU - Thierry Moreau Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p415.abstract N2 - Introduction: Inflammation in chronic obstructive pulmonary diseases (COPD) results in a protease/anti-protease imbalance that leads to a massive release of neutrophil serine proteases (elastase, proteinase 3 and cathepsin G). These proteases stimulate secretion of mucus and pro-inflammatory cytokines. In order to target serine proteases, we designed a recombinant inhibitor derived from trappin-2 which is able to inhibit all three proteases at the same time. The aim of the study was to evaluate the inhibitory, anti-inflammatory and anti-secretory effects of trappin-2 A62L (T2A62L) on lung epithelium exposed to neutrophil serine proteases.Methods: A549 cells were exposed to proteases for 24H with or without addition of T2A62L. Protective effect of T2A62L towards the degradation of cell junctions by proteases was analyzed by immunofluorescence. Levels of mucus secretion were determined by measuring the rate of expression of mucin genes and the anti-inflammatory activity of T2A62L was investigated by measuring the rate of pro-inflammatory mediators release after LPS stimulation.Results: Neutrophil serine proteases proteolytically degrade cellular junctions and increase mucin gene expression. T2A62L added to the culture medium inhibits the degradation of cell junctions proteins (E-cadherin, ZO-1), decreases MUC5AC and MUC5B mRNA expression induced by elastase and IL-6 and IL-8 productions.Conclusion: Our results demonstrate that T2A62L exhibits anti-proteolytic, anti-inflammatory and anti-secretory effects. This new, anti-protease may therefore be of therapeutic value in treating inflammatory lung diseases such as COPD. ER -