Abstract
Objectives: This study is designed to confirm the anti-fibrotic effect of thalidomide on bleomycin-induced lung fibrosis in a mouse model and to identify whether this anti-fibrotic effect is associated with inhibition of the transforming growth factor-β (TGF-β)-induced extracellular signal-regulated kinase1/2 (ERK1/2). Methods and materials: C57BL/6 female mice were administered blomycin sulfate. In cultured human lung fibroblasts, expressions of type I collagen, fibronectin, and either TGF-β or IL-6 were measured after thalidomide treatment by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of ERK1/2, type I collagen, fibronectin, and TGF-β1 from lung tissues of blomycin-induced mice and from mouse lung fibroblasts were evaluated using RT-PCR and western blotting. Results: Thalidomide administration significantly inhibits TGF-β1 mRNA expression in a dose-dependant manner following administration of IL-6 and IL-6R. In the analysis of BAL fluids, total BAL inflammatory cell counts, TGF-β1, and IL-6 levels in thalidomide-treated mice were significantly reduced when compared with bleomycin-treated mice (p < 0.01, p < 0.01, and p < 0.001, respectively). Thalidomide inhibited total ERK1/2 and phospho-ERK1/2 expression after TGF-β1 stimulation in the RT-PCR and western blotting. Conclusion: The results of our study suggest that the anti-fibrotic effect of thalidomide on lung fibrosis may be related to suppression of the TGF-β1-induced ERK1/2 signaling pathway.
| Original language | English |
|---|---|
| Pages (from-to) | 177-188 |
| Number of pages | 12 |
| Journal | Inflammation Research |
| Volume | 59 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2010 Mar 1 |
Fingerprint
Keywords
- Bleomycin
- ERK1/2
- Fibrosis
- Lung
- TGF-β
- Thalidomide
ASJC Scopus subject areas
- Immunology
- Pharmacology
Cite this
Anti-fibrotic effect of thalidomide through inhibiting TGF-β-induced ERK1/2 pathways in bleomycin-induced lung fibrosis in mice. / Choe, Jung Yoon; Jung, Hyun Joo; Park, Ki Yeun; Kum, Yoon Seup; Song, Gwan Gyu; Hyun, Dae Sung; Park, Sung Hoon; Kim, Seong Kyu.
In: Inflammation Research, Vol. 59, No. 3, 01.03.2010, p. 177-188.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-fibrotic effect of thalidomide through inhibiting TGF-β-induced ERK1/2 pathways in bleomycin-induced lung fibrosis in mice
AU - Choe, Jung Yoon
AU - Jung, Hyun Joo
AU - Park, Ki Yeun
AU - Kum, Yoon Seup
AU - Song, Gwan Gyu
AU - Hyun, Dae Sung
AU - Park, Sung Hoon
AU - Kim, Seong Kyu
PY - 2010/3/1
Y1 - 2010/3/1
N2 - Objectives: This study is designed to confirm the anti-fibrotic effect of thalidomide on bleomycin-induced lung fibrosis in a mouse model and to identify whether this anti-fibrotic effect is associated with inhibition of the transforming growth factor-β (TGF-β)-induced extracellular signal-regulated kinase1/2 (ERK1/2). Methods and materials: C57BL/6 female mice were administered blomycin sulfate. In cultured human lung fibroblasts, expressions of type I collagen, fibronectin, and either TGF-β or IL-6 were measured after thalidomide treatment by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of ERK1/2, type I collagen, fibronectin, and TGF-β1 from lung tissues of blomycin-induced mice and from mouse lung fibroblasts were evaluated using RT-PCR and western blotting. Results: Thalidomide administration significantly inhibits TGF-β1 mRNA expression in a dose-dependant manner following administration of IL-6 and IL-6R. In the analysis of BAL fluids, total BAL inflammatory cell counts, TGF-β1, and IL-6 levels in thalidomide-treated mice were significantly reduced when compared with bleomycin-treated mice (p < 0.01, p < 0.01, and p < 0.001, respectively). Thalidomide inhibited total ERK1/2 and phospho-ERK1/2 expression after TGF-β1 stimulation in the RT-PCR and western blotting. Conclusion: The results of our study suggest that the anti-fibrotic effect of thalidomide on lung fibrosis may be related to suppression of the TGF-β1-induced ERK1/2 signaling pathway.
AB - Objectives: This study is designed to confirm the anti-fibrotic effect of thalidomide on bleomycin-induced lung fibrosis in a mouse model and to identify whether this anti-fibrotic effect is associated with inhibition of the transforming growth factor-β (TGF-β)-induced extracellular signal-regulated kinase1/2 (ERK1/2). Methods and materials: C57BL/6 female mice were administered blomycin sulfate. In cultured human lung fibroblasts, expressions of type I collagen, fibronectin, and either TGF-β or IL-6 were measured after thalidomide treatment by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of ERK1/2, type I collagen, fibronectin, and TGF-β1 from lung tissues of blomycin-induced mice and from mouse lung fibroblasts were evaluated using RT-PCR and western blotting. Results: Thalidomide administration significantly inhibits TGF-β1 mRNA expression in a dose-dependant manner following administration of IL-6 and IL-6R. In the analysis of BAL fluids, total BAL inflammatory cell counts, TGF-β1, and IL-6 levels in thalidomide-treated mice were significantly reduced when compared with bleomycin-treated mice (p < 0.01, p < 0.01, and p < 0.001, respectively). Thalidomide inhibited total ERK1/2 and phospho-ERK1/2 expression after TGF-β1 stimulation in the RT-PCR and western blotting. Conclusion: The results of our study suggest that the anti-fibrotic effect of thalidomide on lung fibrosis may be related to suppression of the TGF-β1-induced ERK1/2 signaling pathway.
KW - Bleomycin
KW - ERK1/2
KW - Fibrosis
KW - Lung
KW - TGF-β
KW - Thalidomide
UR - http://www.scopus.com/inward/record.url?scp=77749340411&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77749340411&partnerID=8YFLogxK
U2 - 10.1007/s00011-009-0084-9
DO - 10.1007/s00011-009-0084-9
M3 - Article
C2 - 19757088
AN - SCOPUS:77749340411
VL - 59
SP - 177
EP - 188
JO - Inflammation Research
JF - Inflammation Research
SN - 1023-3830
IS - 3
ER -