Differential modulation of pulmonary caspases: Is this the key to Ureaplasma-driven chronic inflammation?

Although accepted agents in chorioamnionitis and preterm birth, the role of Ureaplasma species (spp.) in inflammation-driven morbidities of prematurity, including the development of bronchopulmonary dysplasia, remains controversial. To add to scarce in vitro data addressing the pro-inflammatory capacity of Ureaplasma spp., pulmonary epithelial-like A549 cells and human pulmonary microvascular endothelial cells (HPMEC) were incubated with Ureaplasma (U . ) urealyticum , U . parvum , and Escherichia coli lipopolysaccharide (LPS). Ureaplasma isolates down-regulated caspase mRNA levels in A549 cells (caspase 8: p <0.001, 9: p <0.001, vs. broth), while increasing caspase protein expression, enzyme activity, and cell death in HPMEC (active caspase 3: p <0.05, caspase 8: p <0.05, active caspase 9: p <0.05, viability: p <0.05). LPS, contrarily, induced caspase mRNA expression in HPMEC (caspase 3: p <0.01, 4: p <0.001, 5: p <0.001, 8: p <0.001, vs. control), but not in A549 cells, and did not affect enzyme activity or protein levels in either cell line. LPS, but neither Ureaplasma isolate, enhanced mRNA expression of pro-inflammatory interleukin ( IL)-6 in both A549 ( p <0.05, vs. control) and HPMEC ( p <0.001) as well as tumor necrosis factor-α ( p <0.01), IL-1β ( p <0.001), and IL-8 ( p <0.05) in HPMEC. We are therefore the first to demonstrate a differential modulation of pulmonary caspases by Ureaplasma spp. in vitro . Ureaplasma -driven enhanced protein expression and activity of caspases in pulmonary endothelial cells result in cell death and may cause structural damage. Down-regulated caspase mRNA in pulmonary epithelial cells, contrarily, may indicate Ureaplasma -induced inhibition of apoptosis and prevent effective immune responses. Both may ultimately contribute to chronic Ureaplasma colonization and long-term pulmonary inflammation.