白细胞介素1β抑制心肌成纤维细胞胶原合成并促进其分解－副本.pdfVIP

Acta Physiologica Sinica , June 25, 2008, 60 (3): 355-361 355 Research Paper Interleukin-1β inhibits collagen synthesis and promotes its decomposition in cultured cardiac fibroblasts XIAO Hua, JI Ai-Min, LI Zhi-Liang, SONG Xu-Dong, SU Dan, CHEN Ai-Hua* Department of Cardiology, the Zhujiang Hospital, Nanfang Medical University, Guangzhou 510282, China Abstract: The present study aimed to investigate the effects of interleukin-1β (IL-1 β) 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 3 H-thymidine ( H-TdR) incorporation and collagen synthesis was measured by 3 3 H-proline ( 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 3H-TdR and 3H-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-1 β (0.01-100 ng/mL) also dose-dependently increased the protein and mRNA expressions of MMP-2 and MMP-9 (P0.05, P0.01), 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-1 β 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 ven