Conclusion
These results suggest that pressure stress delays IL-1β-induced COX-2 expression via the delayed activation of MAPKs in PASMCs, and the effects of pressure stress differ according to the bioactive substance being stimulated. Our results demonstrate that the application of pressure stress to PASMCs directly alters cell function, which may provide a basic insight into our understanding of the pathogenesis of PH.
Methods
Either 20 or 60 mmHg atmospheric pressure was applied to PASMCs by a pressure-loading apparatus. Protein expression and phosphorylation were analyzed by western blotting. mRNA expression was analyzed by quantitative real-time reverse transcription-polymerase chain reaction.
Results
IL-1β-induced COX-2 protein expression peaked at 6 h in non-pressurized cells, whereas COX-2 expression was delayed, peaking at 12 h, in 20 and 60 mmHg pressurized cells. Both pressures also delayed the time to peak COX-2 mRNA expression induced by IL-1β. In addition, pressure stress delayed the time to peak mitogen-activated protein kinase (MAPK) phosphorylation induced by IL-1β. In contrast, angiotensin II-induced transient COX-2 mRNA expression and MAPK phosphorylation were not affected by pressure stress.