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

Sheng Li Xue Bao. 2008 Jun 25;60(3):355-61.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Collagen / biosynthesis*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Interleukin-1beta / pharmacology*
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Myocardial Infarction
  • Myocardium / cytology
  • Rats
  • Rats, Sprague-Dawley
  • Ventricular Remodeling

Substances

  • Interleukin-1beta
  • Collagen
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat