Pathogenicity of Pseudomonas aeruginosa infections can be heavily influenced by the host inflammatory responses. P. aeruginosa secretes several extracellular products such as lipopolysaccharide, exotoxin A, and elastase. This bacterium is widely studied in acute and chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and Cystic Fibrosis (CF). In order to understand part of the underlying mechanism, we focused on the role of Pseudomonas aeruginosa elastase (PE) in provoking the host inflammatory response in an in vitro model. We hypothesized that PE stimulates cytokine and chemokine production by activating mitogen activated protein kinase (MAPK) cascade through nuclear factor kappa B (NFkB). We used biochemical, as well as immunological techniques, to confirm or reject our hypothesis. We found that PE provokes the fibroblast through the epidermal growth factor receptor (EGFR) which leads to the activation of the extracellular signal-regulated kinase (ERK) arm of the MAPK and translocation of NFkB to the nucleus. Our data indicate that PE stimulates gene and protein expression of the proinflammatory cytokine interleukin 8 (IL-8) through the MAPK pathway. Furthermore, the use of specific inhibitors of EGFR, MEK, and NFkB, AG 1478, U0126, and BAY 11-7085 respectively, confirmed the hypothesis. The study confirms the importance of PE in P. aeruginosa induced infection and inflammation in the human lungs.
Date of publication
Bass, Kourtney, "Molecular Mechanism of Cytokine Production by Human Lung Fibroblast in Response to Pseudomonas Aeruginosa Elastase" (2015). Biology Theses. Paper 17.