Thalidomide has a therapeutic effect on interstitial lung fibrosis: evidence from in vitro and in vivo studies.
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.
Zhao
L
L
Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xiao
K
K
Wang
H
H
Wang
Z
Z
Sun
L
L
Zhang
F
F
Zhang
X
X
Tang
F
F
He
W
W
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
D000199:Actins; D024061:Collagen Type III; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D013792:Thalidomide; D006909:Hydroxyproline