Pseudomonas aeruginosa elastase induces IL-8 production in the lung cells via the epidermal growth factor/extracellular signal-regulated proteins/NFκB pathway

We utilized western blot analysis to detect phosphorylation of EGFR and signal transduction intermediates. Northern blot and ELISA analyses were used to determine IL-8 RNA expression and cytokine secretion.We found that the enzymatically active PE enhances IL-8 mRNA and protein secretion but does not increase IL-10 or TNF expression. PE induces phosphorylation of the EGFR and the extracellular signal-regulated proteins (ERK1/2) of the MAPK pathway. Pretreatment of the cells with neutralizing antibody to EGFR or the EGFR-specific tyrphostin AG1478 markedly attenuated the PE-induced ERK1/2 activation. PE-induced IL-8 expression is also abolished in the presence of the MEK inhibitor U0126, indicating the involvement of ERK1/2 in this process.Taken together, the results show PE could modulate lung inflammation by exploiting the EGFR/ERK/NFκB pathway and enhancing IL-8 production by lung fibroblasts.