Pseudomonas aeruginosa Induce Spatio-temporal Secretion of IL-1β, TNFα, proMMP-9, and Reduction of Epithelial e-cadherin in Human Alveolar Epithelial type II (A549) cells.

Abstract

Pseudomonas aeruginosa, is an opportunistic bacterium with hight prevalence in diverse pulmonary infections. Although several genes have been involved in the resistance and evasion system of the immunological response of the host, little information is known about the inflammatory, degradative, and cell binding response induced by P. aeruginosa on human lung alveolar epithelial cells. The purpuse of this study was dtermine the cytokine expression (IL-1β, and TNFα), pro matrix metalloproteinase activaction (proMMP-2 and proMMP-9), and the effects on the cell-binding adhesion protein (E-cadherin) in an in vitro model of human lung alveolar epithelial cells. A549 cells were stimulated with different colony-forming units of P. aeruginosa for 3, 6, and 24 hours. After these times, culture media was collected, IL-1β and TNFα were evaluated by ELISA; proMMP-2 and -9 were determined by substrate gel zymography; and the isoform of actMMP-9 and E-cadherin assessed by immunoreactivity on A549 cells. Our results demonstrate that P. aeruginosa induces mainly the secretion of TNFα, increasing the actMMP-9, and significantly reduces the level of E-cadherin in the A549 cells. In summary, the inflammatory/degradative process induced by P.aeruginosa modulates the expression of the E-cadherin protein. The probable clinical implications of this study suggests the use of inhibitos that reduced the degradative activity of proMMP-9 wich will be demonstrated in the next phase of this study.