Hong Kong Med J 2014;20(Suppl 4):S14-7
Cellular signalling pathways of matrix metalloproteinase gene expression by Pseudomonas aeruginosa–infected human bronchial epithelial cells
WS Hui,SP Ho,AT Wong,PL Ho,JCW Mak
Division of Respiratory and Critical Care Medicine, Department of Medicine, The University of Hong Kong
1. Pseudomonas aeruginosa infection is associated with increased production of matrix metalloproteinase-9 (MMP-9) from the airway epithelium; inappropriate expression and activation of MMP-9 may be associated with tissue injury and airway remodelling.
2. P aeruginosa exposure induces the phosphorylation of ERK, JNK, and p38 MAPKs in human airway epithelial cell line (BEAS-2B). Inhibition of ERK or JNK activity blocks IL-8 and MMP-9 mRNA and protein expression in BEAS-2B cells infected with P aeruginosa.
3. Induction of IL-8 and MMP-9 in human bronchial epithelial cells by P aeruginosa infection is mediated via the NF-_B-mediated pathway, possibly through upstream ERK and JNK MAPK pathways.
4. P aeruginosa infection initiates an intense inflammatory response, such as the release of IL-8, which progressively destroys pulmonary tissue via MMP-9 activation and is associated with high mortality.
5. Inhibition of ERK or JNK may be an effective therapeutic strategy against the early stages of pulmonary P aeruginosa infection, via attenuation of the inflammatory cascade.