Small molecular weight secretory factors from Pseudomonas aeruginosa have opposite effects on IL-8 and RANTES expression by human airway epithelial cells

Pseudomonas aeruginosa is an opportunistic human pathogen that causes both an acute lung disease in patients with hospital-acquired pneumonia and a ch ronic lung disease in individuals with cystic fibrosis. Many of the patho p hysiologic effects of P. aeruginosa infection are due to factors secreted b y the bacterium. Conditioned media from cultures of P. aeruginosa increased interleukin-8 expression and decreased regulated on activation, normal T c ells expressed and secreted (RANTES) expression by human airway epithelial cells. Both of these activities were present in heat-treated, protease-trea ted, small molecular weight fractions. The activities were not inhibited by polymyxin B and were not extracted into ethyl acetate, suggesting that the y were not due to endotoxin or autoinducer. Conversely, results from chloro form extractions and studies with a phenazine-minus mutant suggested that t he blue pigment pyocyanin contributes to these activities when present. In addition to the effects of small molecular weight factors on cytokine expre ssion, proteases in bacterial-conditioned media further decreased levels of RANTES. By altering expression, release, and/or activity of inflammatory c ytokines, secretory factors from P. aeruginosa could disrupt the delicate b alance that constitutes the immune response to bacterial infection and thus could contribute to the lung damage that occurs in P. aeruginosa-infected airways.