Modulators of Airway Remodeling: The Role of Caffeine and Calcitriol

Airway remodeling is a process that occurs in chronic obstructive diseases, such as asthma and COPD. It is associated with adverse changes in the structure and function of the airways. An increasing amount of literature points to the potential protective effects of vitamin D and caffeine against inflammation and fibrosis. The aim of the study is to evaluate the effect of calcitriol and caffeine on the expression of genes and proteins associated with airway remodeling. The Calu-3 cell line was treated with TGF-β, calcitriol, and caffeine in different combinations. Subsequently, the expression of VDR, CDH1, VIM, MMP-2, and MMP-9 were examined at the mRNA and protein levels using real-time PCR and Western blot, respectively. One-way analysis of variance was used to determine differences in several groups. Both calcitriol and caffeine were associated with a decrease in the expression of MMP-2 and VIM in TGF-β-treated cells (p = 0.01 and p = 0.006, respectively). Both compounds also reduced the expression of MMP-9 in comparison to TGF-β alone (p = 0.03), though the changes in MMP-9 protein levels did not reach statistical significance. Calcitriol was associated with a decrease in CDH1 expression at both levels in comparison to TGF-β (p < 0.0001 and p = 0.02, respectively). A potential synergistic effect was demonstrated for CDH1 at the mRNA level and for the vitamin D receptor at the protein level. Both vitamin D and caffeine may influence the pathways involved in airway remodeling. Preliminary in vitro findings suggest a potential role of these substances for future therapeutic strategies targeting obstructive diseases; however, the observations require confirmation in further in vivo studies.