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Interleukin--1#beta# inhibits collagen synthesis and promotes its decomposition in cultured cardiac fibroblasts

Xiao Hua, Ji Aimin, Li Zhiliang, Song Xudong, Su Dan, Chen Aihua

Department of Cardiology,the Zhujiang Hospital,Nanfang Medical University.Guangzhou 510282,Guangdong

Abstract

The present study aimed to investigate the effects of intereukin-1#beta# at different doses on collagen synthesis and decomposition in cultured cardiac fibroblasts in neonatal Sprague-Dawley rat. Cardiac fibroblasts were treated with IL-1#beta# (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 reversed transcription-ploymerase 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-1#beta# groups (≥0.1 ng/mL) but not in low-dose IL-1#beta# group (0.01 ng/mL). IL-1#beta# significantly increased MMP-2 and MMP-9 activities. IL-1#beta# also dose-dependently increased the protein expressions of MMP-2 (fold change; 0.01 ng/mL: 1.35±0.05; 0.1 ng/mL: 1.56±0.10; P<0.05; 1 ng/mL: 2.15±0.32; 10 ng/mL: 2.34±0.19; 100 ng/mL: 2.41±0.26; P<0.01) and MMP-9 (fold change; 0.01 ng/mL: 1.38±0.20, P<0.05; 0.1 ng/mL: 2.37±0.21; 1 ng/mL: 2.56±0.31; 10 ng/mL: 2.60±0.19; 100 ng/mL: 2.67±0.15; P<0.01), respectively. Similar results were observed in mRNA expression of MMP-2 (fold change; 0.01 ng/mL: 1.81±0.16, P<0.05; 0.1 ng/mL: 2.17±0.19; 1 ng/mL: 2.18±0.04; 10 ng/mL: 2.27±0.06; 100 ng/mL: 2.31±0.07; P<0.01) and MMP-9 (fold change; 0.01 ng/mL: 1.36±.13; P<0.05; 0.1 ng/mL: 1.49±0.08; 1 ng/mL: 1.50±0.11; 10 ng/mL: 1.51±0.24; 100 ng/mL: 1.52±0.31; P<0.01). These results suggest that IL-1#beta# decreases collagen synthesis and activates MMPs through transcriptional and posttranslational processes via degrading collagen in a dose-dependent way. Elevation of IL-1#beta# after myocardial infarction is possibly involved in the process of post-myocardial infarction ventricle remodeling, and the concentration of IL-1#beta# is possibly a major factor which affects the degree of ventricle remodeling.

Key words: interleukin-1#beta#;Fibroblasts;collagen;matrix metalloproteinases

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Citing This Article：

Xiao Hua, Ji Aimin, Li Zhiliang, Song Xudong, Su Dan, Chen Aihua. Interleukin--1#beta# inhibits collagen synthesis and promotes its decomposition in cultured cardiac fibroblasts. Acta Physiol Sin 2008; 60 (3): 355-361 (in Chinese with English abstract).