RT Journal Article
SR Electronic
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
FD European Respiratory Society
SP p415
VO 38
IS Suppl 55
A1 Annabelle Tanga
A1 Alhame Saidi
A1 Sandrine Dallet-Choisy
A1 Marie-Louise Zani
A1 Thierry Moreau
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p415.abstract
AB 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.