Interleukin-1β inhibits collagen synthesis and promotes its decomposition in cultured cardiac fibroblasts.
The present study aimed to investigate the effects of interleukin-1β (IL-1β) at different doses on collagen synthesis and decomposition in cultured cardiac fibroblasts from neonatal Sprague-Dawley rat. Cardiac fibroblasts were treated with IL-1β (0.01, 0.1, 1, 10, 100 ng/mL) for 24 h. Cell DNA synthesis was measured by (3)H-thymidine ((3)H-TdR) incorporation and collagen synthesis was measured by (3)H-proline ((3)H-Pro) incorporation. Matrix metalloproteinase (MMP) activity was measured by gelatinase zymography. MMP-2, MMP-9 protein expressions were measured by Western blot. mRNA expressions of MMP-2 and MMP-9 were detected by reverse transcription-polymerase chain reaction (RT-PCR). Compared with that in the control group, the incorporation of (3)H-TdR and (3)H-Pro decreased in high-dose IL-1β groups (≥0.1 ng/mL) but not in low-dose IL-1β group (0.01 ng/mL). IL-1β significantly increased MMP-2 and MMP-9 activities. IL-1β (0.01-100 ng/mL) also dose-dependently increased the protein and mRNA expressions of MMP-2 and MMP-9 (P<0.05, P<0.01), respectively. These results suggest that IL-1β decreases collagen synthesis and MMP activities through transcriptional and posttranslational processes via degrading collagen in a dose-dependent way. Elevation of IL-1β is possibly involved in the process of ventricular remodeling after myocardial infarction, and the concentration of IL-1β is possibly a major factor which affects the extent of ventricular remodeling.
Department of Cardiology, the Zhujiang Hospital, Nanfang Medical University, Guangzhou 510282, China.
Hua
H
Xiao
Ai-Min
AM
Ji
Zhi-Liang
ZL
Li
Xu-Dong
XD
Song
Dan
D
Su
Ai-Hua
AH
Chen
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009203:Myocardial Infarction; D009206:Myocardium / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling
D053583:Interleukin-1beta; D003094:Collagen; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat