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 activ... More
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.
