title: Thalidomide has a therapeutic effect on interstitial lung fibrosis: evidence from in vitro and in vivo studies.
abstract: The objective of this study was to investigate the effects of thalidomide (THD) on interstitial lung fibrosis (ILF). In vitro, human fetal lung fibroblast (HFL-F) to myofibroblast (MF) trans-differentiation was induced by transforming growth factor (TGF)-beta1. The effects of THD on trans-differentiation process or differentiated MF were evaluated by measuring hydroxyproline (HYP) content by alkaline hydrolysis colorimetry, alpha-smooth muscle actin (alpha-SMA) protein by Western blot and alpha-SMA and pro-collagen III mRNA expressions by semi-quantitative reverse transcription-polymerase chain reaction; in vivo, a mouse model of ILF was generated by daily subcutaneous injection of bleomycin (BLM) in female C3H mice. Gastric perfusion of THD began 1 week prior to injection and lasted for 8 weeks. Lung specimens were harvested at different time-points (1, 4, 6 and 8 weeks) for pathology and immunohistochemistry examination. The HYP content, alpha-SMA and pro-collagen III mRNA expressions were also assessed. THD inhibited the up-regulation of HYP protein, pro-collagen III mRNA and alpha-SMA protein induced by TGF-beta1 in HFL-F cells, and additionally inhibited pro-collagen III mRNA expression on trans-differentiated MF. THD reduced HYP synthesis in the lung tissues of BLM-treated mice at week 4, and slightly reduced the numbers of alpha-SMA-positive cells. THD had an effect on ILF models both in vitro and in vivo.
authors: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: L
authors: L
authors: Zhao
authors: K
authors: K
authors: Xiao
authors: H
authors: H
authors: Wang
authors: Z
authors: Z
authors: Wang
authors: L
authors: L
authors: Sun
authors: F
authors: F
authors: Zhang
authors: X
authors: X
authors: Zhang
authors: F
authors: F
authors: Tang
authors: W
authors: W
authors: He
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D001761:Bleomycin; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D024061:Collagen Type III / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D006909:Hydroxyproline / Q000235:genetics; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000494:pharmacology
chemical_list: D000199:Actins; D024061:Collagen Type III; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D013792:Thalidomide; D006909:Hydroxyproline