Vilela Polyana das Graças Figueiredo, de Oliveira Jonatas Rafael, de Barros Patrícia Pimentel, Leão Mariella Vieira Pereira, de Oliveira Luciane Dias, Jorge Antonio Olavo Cardoso
Laboratory of Microbiology and Immunology, Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, Univ. Estadual Paulista, UNESP, São José dos Campos, SP, Brazil.
Bioscience Basic Institute, University of Taubaté, Taubaté, SP, Brazil.
Arch Oral Biol. 2015 Sep;60(9):1196-202. doi: 10.1016/j.archoralbio.2015.04.009. Epub 2015 May 21.
The role of matrix metalloproteinases (MMPs) in tissue degradation has become evident in many diseases and great interest therefore exists in the pharmacological control of the activity of these enzymes. This study evaluated the effect of caffeic acid phenethyl ester (CAPE) on the production of MMPs and their inhibitor (TIMP) in monocytes activated by lipopolysaccharide (LPS).
The human monocytic cell line (THP-1) was treated with non-cytotoxic concentrations of CAPE (10 and 60μM) combined with 1μg/mL of LPS. The gene expression of MMP-1, MMP-9 and TIMP-1 was evaluated by quantitative real-time polymerase chain reaction. The protein secretion into the culture medium was assessed via enzyme-linked immunosorbent assay and the gelatinolytic activity of MMP-9 by zymography.
CAPE, especially at the highest concentration, down-regulated MMP-1 and MMP-9 gene expression but up-regulated the gene expression of TIMP-1. Furthermore, CAPE reduced the secreted protein level of MMP-1 and MMP-9 as well as the gelatinolytic activity of MMP-9.
CAPE was able to inhibit the gene expression, production and the activity of MMPs induced by LPS and also increased the gene expression of TIMP-1. The present observations suggest that CAPE exerted a positive effect on the regulatory mechanism between MMPs and TIMP, which is important for the control of different diseases.
基质金属蛋白酶（MMPs）在组织降解中的作用在许多疾病中已变得明显，因此人们对这些酶活性的药理控制非常感兴趣。本研究评估了咖啡酸苯乙酯（CAPE）对脂多糖（LPS）激活的单核细胞中MMPs及其抑制剂（TIMP）产生的影响。
用人单核细胞系（THP-1）处理非细胞毒性浓度的CAPE（10和60μM）并联合1μg/mL的LPS。通过定量实时聚合酶链反应评估MMP-1、MMP-9和TIMP-1的基因表达。通过酶联免疫吸附测定评估培养基中的蛋白分泌，并通过酶谱法评估MMP-9的明胶溶解活性。
CAPE，尤其是在最高浓度时，下调MMP-1和MMP-9基因表达，但上调TIMP-1的基因表达。此外，CAPE降低了MMP-1和MMP-9的分泌蛋白水平以及MMP-9的明胶溶解活性。
CAPE能够抑制LPS诱导的MMPs的基因表达、产生和活性，还增加了TIMP-1的基因表达。目前的观察结果表明，CAPE对MMPs和TIMP之间的调节机制发挥了积极作用，这对控制不同疾病很重要。
