Caffeine inhibits TGF? activation in epithelial cells, interrupts fibroblast responses to TGF?, and reduces established fibrosis in ex vivo precision-cut lung slices

Tatler, Amanda L.; Barnes, Josephine; Habgood, Anthony; Goodwin, Amanda; McAnulty, Robin; Jenkins, Gisli

Abstract

Caffeine is a commonly used food additive found naturally in many products. In addition to potently stimulating the central nervous system caffeine is able to affect various systems within the body including the cardiovascular and respiratory systems. Importantly, caffeine is used clinically to treat apnoea and bronchopulmonary dysplasia in premature babies. Recently, caffeine has been shown to exhibit antifibrotic effects in the liver in part through reducing collagen expression and deposition, and reducing expression of the profibrotic cytokine TGF?. The potential antifibrotic effects of caffeine in the lung have not previously been investigated. Using a combined in vitro and ex vivo approach we have demonstrated that caffeine can act as an antifibrotic agent in the lung by acting on two distinct cell types, namely epithelial cells and fibroblasts. Caffeine inhibited TGF? activation by lung epithelial cells in a concentration-dependent manner but had no effect on TGF? activation in fibroblasts. Importantly, however, caffeine abrogated profibrotic responses to TGF? in lung fibroblasts. It inhibited basal expression of the ?-smooth muscle actin gene and reduced TGF?-induced increases in profibrotic genes. Finally, caffeine reduced established bleomycin-induced fibrosis after 5?days treatment in an ex vivo precision-cut lung slice model. Together, these findings suggest that there is merit in further investigating the potential use of caffeine, or its analogues, as antifibrotic agents in the lung.

• Journal Article Type: Article
• Acceptance Date: Feb 1, 2016
• Online Publication Date: Feb 24, 2016
• Publication Date: Jun 1, 2016
• Deposit Date: Feb 14, 2018
• Publicly Available Date: Jan 24, 2019
• Print ISSN: 0040-6376
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 71
• Issue: 6
• Pages: 565-567
• DOI: https://doi.org/10.1136/thoraxjnl-2015-208215
• Public URL: https://nottingham-repository.worktribe.com/output/1111072
• Publisher URL: https://thorax.bmj.com/content/71/6/565