@article {Georgep3335, author = {Peter M. George and Rekha Badiger and Hime Gashaw and Neil Galloway-Phillipps and Trevor T. Hansel and Jane A. Mitchell}, title = {Effects of type I, II and III interferons on endothelin-1 release by human pulmonary artery smooth muscle cells}, volume = {38}, number = {Suppl 55}, elocation-id = {p3335}, year = {2011}, publisher = {European Respiratory Society}, abstract = {The potent vasoconstrictor and mitogen peptide endothelin-1 (ET-1) is a therapeutic target for the treatment of pulmonary hypertension. Work from our group has shown that ET-1 release by human pulmonary artery smooth muscle cells (HPASMCs) is critically regulated by interferons (IFN) and TNF. We have shown that type I IFNα and IFNβ and type II IFNγ, but not type III IFNλ, all released in host responses to viral infection, induce ET-1. As viral infection and IFN therapy are increasingly associated with lung toxicity, including pulmonary hypertension, we have investigated the nature of any interaction between IFNs for ET-1 release by HPASMCs. Cells from 3 separate donors were stimulated in 96-well plates with IFNα, -β, -γ and -λ (all 10ng/ml). Supernatants were collected after 24 hours and ET-1 concentrations measured by sandwich ELISA. In the presence of TNFα (10ng/ml), type I IFNs (-α and -β) or type II IFNγ, but not type III IFNλ, induced ET-1 release. Additive release of ET-1 was seen with IFNα/γ and IFNβ/γ but not IFNα/β. IFNλ did not release ET-1 under any condition studied. Type I and II IFNs act independently to stimulate ET-1 from HPASMCs, which reflects what is known about their separate receptor pathways.Figure 1. Data is mean {\textpm} SEM. *P\<0.05 one-way ANOVA for combination of IFNs v IFNs alone.Our finding that IFNλ is inactive in these cells may suggest that type III IFN spares the lung vasculature.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/38/Suppl_55/p3335}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }