[Inhibition of human lung fibroblast proliferation and the mitogen activated protein kinase pathway by dexamethasone].
OBJECTIVE
To investigate the effects of dexamethasone on human lung fibroblast cell proliferation, cell cycles, and cell mitogen-activated protein kinases (MAPKs) passway.


METHODS
Dexamethasone was used at various concentration in culture medium. Cell number was counted using a hemacytometer. Whole cell propidium iodide staining and flow cytometric analysis were performed to determine cellular DNA content. MAPK proteins and activation were tested by Western blot analysis with antibodies to c-Jun N-terminal kinase (JNK), phospho-JNK, extracellular signal-regulated kinase (ERK), phospho-ERK, p38 and phospho-p38.


RESULTS
1x10(-7) mol/L and 1x10(-6) mol/L dexamethasone suppressed the proliferation of lung fibroblast cells by 34% and 72%, respectively, than that of control. This suppression was dose-dependant. Dexamethasone suppressed cell cycle with accumulation of cells in G1/G0 stage. It increased from 81.9% to 90.1% compared with that of control. We did not find any apoptosis induced by dexamethasone for lung fibroblast cells. Using Western blot analysis, we found that dexamethasone resulted in decreased activity of ERK, but had no effects on JNK and p38.


CONCLUSIONS
Dexamethasone may suppresses the proliferation of lung fibroblast cells, which is partly resulted from the facts that it can inhibit ERK activation in MAPK-signaling pathway but has little effect on JNK and p38 pathway. Dexamethasone may not induce lung fibroblast cell apoptosis directly.
Guo
Zi-jian
ZJ
Department of Respiratory Disease, PUMC Hospital, CAMS and PUMC, Beijing 100730, China. guozj@pumch.ac.cn
Zhu
Yuan-jue
YJ
Gu
Li
L
Zhou
Xin
X
Li
Li-jun
LJ
Tian
Xin-lun
XL
Yao
Wei
W
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects*
D003907:Dexamethasone; D020929:Mitogen-Activated Protein Kinase Kinases