PT  - JOURNAL ARTICLE
AU  - Shu Hisata
AU  - Shigeki Chiba
AU  - Takafumi Ito
AU  - Masahito Ebina
AU  - Toshihiro Nukiwa
TI  - Anti-fibrotic effects of liver X receptor agonists in human fetal lung fibroblasts
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p3804
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p3804.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p3804.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Introduction: Idiopathic pulmonary fibrosis is a progressive life-threatening disease for which anti-inflammatory agents such as glucocorticoids have no therapeutic effect. Liver X receptors (LXRs), which are nuclear receptors activated by oxysterols as natural ligands, show similar tissue-distribution patterns with glucocorticoid receptor and peroxisome proliferator-activated receptor (PPAR)-γ. LXRs play important roles not only in cholesterol metabolism and triglyceride synthesis, but also in inflammation and innate immunity. Previous studies showed anti-fibrotic effects of PPARγ agonists, but it remains unknown whether LXR agonists have anti-fibrotic abilities.Aims: The aim of our current study is to analyze anti-fibrotic effects of LXR agonists on human lung fibroblast.Methods: Serum-deprived MRC5 cells (human fetal lung fibroblast cell line) were pre-incubated with synthetic LXR agonist T0901317 and natural agonist 22(R)-hydroxycholesterol, and were differentiated into myofibroblasts by TGF-β1 for 48 hours. Changes in α-smooth muscle actin (α-SMA) and phosphorylated-Smad2/3 were analyzed by western blot. The inhibitory effects of irreversible PPARγ antagonist GW-9662 on anti-fibrotic abilities of LXR agonists were also examined.Results: LXR agonist T0901317 and 22(R)-hydroxycholesterol inhibited TGF-β1-driven myofibroblast-differentiation as determined by α-SMA by western blot. T0901317 did not inhibit Smad2/3 phosphorylation. An irreversible PPARγ antagonist GW-9662 did not reverse the inhibition of myofibroblast-differentiation by T0901317.Conclusion: LXR agonists have novel and potent anti-fibrotic effects in human lung fibroblasts.