title: In vitro effect of caffeic acid phenethyl ester on matrix metalloproteinases (MMP-1 and MMP-9) and their inhibitor (TIMP-1) in lipopolysaccharide-activated human monocytes.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. Electronic address: polyanafigueiredo@gmail.com.
authors.forename: Polyana das Graças Figueiredo
authors.initials: Pd
authors.lastname: Vilela
authors.affiliation: 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. Electronic address: jroliveira16@hotmail.com.
authors.forename: Jonatas Rafael
authors.initials: JR
authors.lastname: de Oliveira
authors.affiliation: 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. Electronic address: barrosdnapp@yahoo.com.br.
authors.forename: Patrícia Pimentel
authors.initials: PP
authors.lastname: de Barros
authors.affiliation: Bioscience Basic Institute, University of Taubaté, Taubaté, SP, Brazil. Electronic address: mariellaleao@yahoo.com.br.
authors.forename: Mariella Vieira Pereira
authors.initials: MV
authors.lastname: Leão
authors.affiliation: Laboratory of Biochemistry and Pharmacology, Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, Univ. Estadual Paulista, UNESP, São José dos Campos, SP, Brazil. Electronic address: luciane@fosjc.unesp.br.
authors.forename: Luciane Dias
authors.initials: LD
authors.lastname: de Oliveira
authors.affiliation: 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. Electronic address: olavojorge@fosjc.unesp.br.
authors.forename: Antonio Olavo Cardoso
authors.initials: AO
authors.lastname: Jorge
mesh_terms: D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: D002109:Caffeic Acids; D008070:Lipopolysaccharides; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: CAPE; Lipopolysaccharide; Matrix metalloproteinases; Monocytes