title: [Effect of cyclophilin A on monocyte-derived foam cells].
abstract: OBJECTIVE
  To observe whether cyclophilin A (CypA)has an effect on macrophage-derived foam cells, and to investigate the involvement of CypA in the development of atherosclerosis.
  
  
  METHODS
  The foam cell model was established through incubating the human monocyte line (THP-1 cells) with oxidized low density lipoproteins (ox-LDL). The cells were stained with fresh oil red O to study the morphology of the macrophage-derived foam cells. The cell adhesion, invasion and the production of matrix metalloproteinase (MMPs) of the macrophage-derived foam cells were detected by adhesion assay, invasion assay and gelatin zymography respectively both in the absence or presence of different concentrations of purified CypA (50, 100, 200 μg/L). Then the foam cells were respectively pre-treated with CsA, c7b8f10, HAb18 mAb, and dual treatment of c7b8f10 and HAb18 mAb respectively, to investigate the inhibitory effect on macrophage-derived foam cells.
  
  
  RESULTS
  The adhesion, invasion and the production of MMP-9 and MMP-2 were enhanced during the differentiation of monocytes into macrophages (P<0.05). CypA, especially in the concentration of 100 ng/mL, significantly promoted the function of macrophage-derived foam cells (P<0.05). CsA, c7b8f10, HAb18 mAb, and c7b8f10- HAb18 mAb combination dramatically inhibited the function of macrophage-derived foam cells both in the absence or presence of CypA (P<0.05). The c7b8f10- HAb18 mAb combination pretreatment had the most obviously suppressive effect on macrophage-derived foam cells (P<0.05).
  
  
  CONCLUSIONS
  These findings suggest that CypA up regulates the adhesion, the invasion and the expressions of MMP-2 and MMP-9 in macrophage-derived foam cells. The CypA effect is blocked by the pretreatment of the different antagonists. This research might suggest the correlation between atherosclerosis pathogenesis and the vulnerability of atherosclerotic plaques, and thus give us some good ideas for atherosclerosis therapy in future.
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. rmy413@163.com
authors.forename: Meng-yao
authors.initials: MY
authors.lastname: Rong
authors.forename: Rui-xue
authors.initials: RX
authors.lastname: Duo
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Cong-hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Fan
authors.forename: Yan-hong
authors.initials: YH
authors.lastname: Wang
mesh_terms: D050197:Atherosclerosis / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D021984:Cyclophilin A / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005487:Foam Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D021984:Cyclophilin A