Endothelial Responses to ICS/LABA Combinations Are Determined Primarily by the Corticosteroid Component

Area of Science:

• Pulmonary medicine
• Cell biology
• Pharmacology

Background:

• Pulmonary microvasculature is crucial for alveolar integrity.
• Direct effects of inhaled corticosteroids (ICS) on pulmonary endothelial cells are not well understood.

Purpose of the Study:

• Investigate the effects of budesonide and formoterol on pulmonary endothelial cell functions.
• Determine the impact on network formation, apoptosis, migration, proliferation, and efferocytosis.

Main Methods:

• Utilized human pulmonary microvascular endothelial cells (HPMEC-ST1.6R), A549 alveolar epithelial cells, and phagocytic cell models.
• Assessed endothelial network formation, apoptosis markers (caspase-3/7), wound closure, proliferation, spheroid integrity, and efferocytosis.
• Measured epithelial secretion of angiogenic mediators (VEGF, IL-8, MCP-1) and inflammatory cytokines (TNF-α, IL-6).

Main Results:

• Budesonide, alone or with formoterol, reduced endothelial network complexity and epithelial pro-angiogenic mediator secretion.
• Fluticasone propionate demonstrated a similar effect on the epithelial secretome, indicating a class effect.
• Budesonide protected endothelial cells from apoptosis, enhanced efferocytosis, and accelerated wound closure without affecting proliferation.
• Formoterol alone had minimal impact and did not consistently augment budesonide's effects.

Conclusions:

• In vitro, the corticosteroid component predominantly drives pulmonary endothelial cell responses to ICS/LABA combinations.
• ICS suppress pro-angiogenic mediator secretion while promoting endothelial cell survival and repair.
• Findings are hypothesis-generating and require further validation in primary cells and in vivo models.