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.