title: ATF3 Inhibits Tenascin-C-induced Foam Cell Formation in LPS-Stimulated THP-1 Macrophages by Suppressing TLR-4.
abstract: OBJECTIVE
  Efficiently inhibiting the formation of macrophage foam cells is indispensable for mitigating and treating atherosclerosis. Tenascin-C (TN-C) plays an important role in promoting atherosclerosis; therefore, it is essential to inhibit foam cell formation associated with TN-C for controlling atherosclerosis. Activating transcription factor 3 (ATF3) is one of the factors involved in regulating the complex process of foam cell formation. This study aimed to explore the role of TN-C and ATF3 in LPS-stimulated THP-1-derived macrophages.
  
  
  METHODS
  RT-PCR was used for evaluating the expression of TN-C in LPS-stimulated THP-1 macrophages. Further, exogenous TN-C was introduced and incubated with cultured THP-1 macrophages to confirm the effect of TN-C on LPS-stimulated THP-1 macrophages. ATF3-modified THP-1 macrophages were constructed and verified by western blot. High performance liquid chromatography (HPLC) assay and Oil red O staining were applied for detecting cholesteryl ester/total cholesterol (CE/TC) and lipid formation in THP-1 macrophages.
  
  
  RESULTS
  The expression of TN-C was determined to be upregulated in LPS-stimulated THP-1 macrophages in a dose- and time-dependent manner. HPLC assay and Oil red O staining confirmed that TN-C can enhance LPS-induced THP-1 macrophage foam cell formation. Moreover, ATF3 can act as a negative regulatory factor for inhibiting TN-C-induced foam cell formation by suppressing TLR-4 in LPS-stimulated THP-1 macrophages.
  
  
  CONCLUSIONS
  ATF3 can inhibit TN-C-induced foam cell formation in LPS-stimulated THP-1 macrophages by suppressing TLR-4. It may be a useful molecular target to control TN-C-induced foam cell formation in atherosclerosis.
authors.affiliation: Key Disciplines Laboratory Clinical-Medicine Henan, Department of Cardiovascular Surgery, the First Affiliated Hospital of Zhengzhou University.
authors.forename: Hong
authors.initials: H
authors.lastname: Luo
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Chenhui
authors.initials: C
authors.lastname: Qiao
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry; D005487:Foam Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019063:Tenascin / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C495345:TLR4 protein, human; D019063:Tenascin; D051197:Toll-Like Receptor 4; D002784:Cholesterol