Niclosamide is a commonly used helminthicidic drug for the treatment of human parasitosis by helminths. Recently, efforts have been focusing on repurposing this drug for the treatment of other diseases, such as
idiopathic pulmonary fibrosis. Subepithelial lung myofibroblasts (SELMs) isolated from tissue biopsies of patients undergoing surgery for
lung cancer were stimulated with TNF-α (50 ng/mL), IL-1α (5 ng/mL), added alone or in combination, and TGF-β1 (5 ng/mL).
After treatment with
niclosamide at 30 nM and 100 nM concentrations, expression of
collagen type I,
collagen type III, and
fibronectin was studied by total
RNA isolation and qRT-PCR and
protein collagen secretion with the use of Sircol
collagen assay. The migration of SELMs was assessed by a wound-healing assay.
Niclosamide had no effect on baseline SELM fibrotic factor expression. When stimulated with TGF-β1, IL-1α, and/or TNF-α, SELM expression of
collagen type I, type III, and
fibronectin were upregulated, as was the secretion of total
collagen in the culture medium. Treatment with
niclosamide attenuated the effects of
cytokine stimulation leading to a notable decrease in the
mRNA expression of
collagen type I, type III, and
fibronectin in a concentration-dependent manner. SELM
collagen secretion was also reduced by
niclosamide at 100 nM concentration when examined at the
protein level. Migration of both TGF-β1 stimulated and unstimulated SELMs was also inhibited by
niclosamide. In this study, we highlight the anti-fibrotic properties of
niclosamide on SELMs under stimulation with pro-fibrotic and pro-inflammatory
cytokines, thus proposing this compound as a possible new therapeutic agent against lung
fibrosis.