Background. Bronchial smooth muscle cells (BSMC) are a major source of proinflammatory and proangiogenic
cytokines and
chemokines, including
VEGF and
CXC-chemokines.
CXC-chemokines act primarily on neutrophils, mediating their recruitment to and activation at the site of
inflammation. In humans, house-dust mite (HDM)
allergens can cause asthmatic exacerbations and trigger an inflammatory response through
protease-dependent mechanisms. Objective. We investigated the effect HDM extract on the release of pro-angiogenic and proinflammatory
cytokines from BSMC. Methods. 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 measured using a 96-well Boyden chamber. Results. ENA-78/CXCL5
protein levels in
conditioned medium of BSMC stimulated with HDM extract were significantly reduced (n = 10, P < 0.05) but restored in the presence of 5% FCS. HDM extracts did not affect ENA-78/CXCL5
mRNA levels. Recombinant ENA-78/CXCL5 was degraded after incubation with HDM extracts (n = 7, P < 0.05) but restored after the addition of the
serine protease AEBSF. Neutrophil migration towards recombinant ENA-78/CXCL5 was also reduced in the presence of HDM extract. Conclusion. HDM
proteases degrade ENA-78/CXCL5. Thus 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.