Effects of Budesonide on Coronavirus-Associated Receptor and Immune-Mediator Expression in Human Lung Microvascular Endothelial Cells.

Background and Objectives: Inhaled corticosteroids exert broad immunomodulatory effects in patients with chronic airway diseases. However, their direct impact on pulmonary endothelial immune responses and coronavirus-associated receptor expression remains unclear. This study investigated the effects of budesonide on immune responses and the expression of coronavirus entry receptors in human lung microvascular endothelial cells (HMVEC-L). Materials and Methods: HMVEC-L cells were exposed to budesonide (1 ng/mL), a non-cytotoxic concentration selected based on cell viability assays. The mRNA expression of angiotensin-converting enzyme 2 (ACE2), dipeptidyl peptidase-4 (DPP4), aminopeptidase N (AP-N), intercellular adhesion molecule 1 (ICAM-1), interferon beta (IFN-β), RANTES/CCL5, and interleukin-8 (IL-8/CXCL8) was analyzed using quantitative RT-PCR. The surface expression of ACE2, DPP4, AP-N, and ICAM-1 was assessed using flow cytometry. Secreted IL-8 concentration was measured using ELISA. Results: Budesonide significantly reduced AP-N and DPP4 mRNA expression, accompanied by a decrease in the surface expression of both receptors. ACE2 mRNA expression was transiently reduced, whereas ACE2 surface expression was modestly increased by approximately 5% at 72 h. Budesonide also reduced early ICAM-1 mRNA expression but increased its surface expression at the later time point. Budesonide significantly reduced RANTES/CCL5 and IL-8/CXCL8 mRNA expression, with a corresponding decrease in secreted IL-8 concentration, whereas IFN-β mRNA expression showed a non-significant statistical decrease. Conclusions: Budesonide directly modulates pulmonary endothelial immune responses and coronavirus-associated receptor expression. These findings indicate that budesonide modulates the expression of coronavirus-associated receptors and basal antiviral and inflammatory mediators in HMVEC-L cells. Because viral binding, entry, replication, and infection were not assessed, these results should be interpreted as evidence of receptor and immune-mediator modulation rather than as demonstrating altered coronavirus susceptibility.