Effects of nintedanib on unstimulated and stimulated macrophages from human monocytes in single culture and in co-culture with fibroblasts.

Macrophages have emerged as important cells in both promoting and resolving tissue fibrosis. It is thought that macrophages can execute these functionally opposing phenotypes as a result of their ability to dynamically respond to signals in their microenvironment. One approved antifibrotic drug for the treatment of lung fibrosis is nintedanib. Nintedanibs effect has largely been attributed to its inhibitory effect on tyrosine kinases resulting in inhibition of fibroblast proliferation with only very few studies investigating its effects on macrophage phenotypes. This study was carried out to address the anti-fibrotic effect of NTB on macrophage phenotypes in the context of fibroblasts to approximate the tissue environment. Analysis of bulk RNA-Seq samples from human monocyte derived macrophages which have been cultured in either single culture (SiCu_MDM) or co-culture with fibroblasts (CoCu_MDM). Macrophages were obtained from 6 human donors, Fibroblasts were obtained from one donor. The following conditions were evaluated: Untreated +/- Nintedanib (NTB), IL4/IL13 + TNF +/- Nintedanib. All conditions were applied to Macrophages in single culture as well as Macrophages that have been cultured in indirect co-culture with fibroblasts, with six replicates for a total of 48 RNA-Seq samples.