[Tyrosine kinases inhibitor A77 1726 inhibits upregulation of collagen generation in fibroblasts induced by IL-13].
OBJECTIVE
To observe the inhibitory effects of tyrosine kinases inhibitor A77 1726 on collagen generation induced by IL-13 in fibroblasts.


METHODS
The inhibition rate of fibroblast proliferation with different concentration of A77 1726 was observed by MTT method. The fibroblasts were divided into the experimental group (A77 1726 50 micromol/L and IL-13 100 microg/L) and the control group (IL-13 100 microg/L). After 24, 48 and 72 hours, the inhibitory effects of A77 1726 on collagen secretion of fibroblasts investigated by hydroxyproline release assay. The inhibitory effects of A77 1726 on collagen type I alpha1 gene mRNA expression in fibroblasts were examinated by RT-PCR. The influence of A77 1726 on collagen type I synthesis in fibroblasts was analyzed by Western blot.


RESULTS
The proliferation of fibroblasts was inhibited by A77 1726. Total collagen generation was down-regulated after 48 h and 72 h stimulation of A77 1726 (P<0.05). The expression level of collagen type I alpha1 gene mRNA was obviously lower in the experimental group than in the control group after 48 h and 72 h stimulation of A77 1726 (P<0.05). Collagen type I production of fibroblasts treated with A77 1726 for 48 and 72 hours was decreased obviously in the experimental group than in the control group (P<0.05).


CONCLUSIONS
Tyrosine kinases inhibitor A77 1726 has an inhibitory effect on collagen protein synthesis in fibroblasts induced by IL-13.
Xiong
Li-Xia
LX
Department of Pathophysiology, Nanchang University, China. xionglixia8888@yahoo.com.cn
Li
Wen-Lin
WL
Shi
Xiao-Yu
XY
Liu
Zhuo-Qi
ZQ
Tang
Hong-Lin
HL
D016475:3T3 Cells; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D003437:Crotonates; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology*; D051379:Mice; D009570:Nitriles; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014052:Toluidines
D000814:Aniline Compounds; D024042:Collagen Type I; D003437:Crotonates; D004791:Enzyme Inhibitors; D006885:Hydroxybutyrates; D018793:Interleukin-13; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D011505:Protein-Tyrosine Kinases