RT Journal Article
SR Electronic
T1 Proteolytic activity present in house-dust-mite extracts degrades ENA-78/CXCL5 and reduces neutrophil migration
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P4063
VO 44
IS Suppl 58
A1 L. Keglowich
A1 M. Tamm
A1 N. Miglino
A1 P. Borger
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P4063.abstract
AB Bronchial smooth muscle (BSM) cells are a major source of pro-inflammatory and pro-angiogenic cytokines and chemokines, including VEGF and CXC-chemokines. CXC-chemokines act primarily on neutrophils, mediating their recruitment to and activation at the side of inflammation. In humans, house-dust mite (HDM) allergens can cause asthmatic exacerbations and trigger an inflammatory response through protease-dependent mechanisms.We investigated the effect HDM extract on the release of pro-angiogenic and proinflammatory cytokines from BSM cells. Human primary BSMC were stimulated with HDM extract in the absence or presence of fetal calf serum (FCS). Twenty angiogenic cytokines were detected by a specific antibody array and modified protein levels were confirmed by ELISA. Neutrophil migration was detected using a 96-well Boyden chamber.The concentration of ENA-78/CXCL5 in conditioned medium collected from BSMC stimulated with HDM extract was significantly reduced, whereas ENA-78/CXCL5 mRNA levels were not altered. In the presence of 5% FCS the inhibitory effect of HDM on ENA-78/CXCL5 expression was abrogated. Furthermore, recombinant ENA-78/CXCL5 was degraded by incubation with HDM extract, which was prevented by addition of FCS as well as by addition of a serine protease inhibitor. Neutrophil migration towards recombinant ENA-78/CXCL5 was reduced in HDM extract stimulated conditions.We conclude that HDM proteases degrade ENA-78/CXCL5. These data imply that exposure to HDM allergens may alter ENA-78/CXCL5 levels in the lungs and may affect angiogenesis and the inflammatory response in the airways of asthma patients.