title: Interleukin-37 suppresses ICAM-1 expression in parallel with NF-κB down-regulation following TLR2 activation of human coronary artery endothelial cells.
abstract: BACKGROUND
  The inflammatory receptor Toll-like receptors (TLRs) activation could induce endothelial inflammatory responses, which plays an important role in the development of many diseases including atherosclerosis. We already found that TLR2 activation of Peptidoglycan (PGN) stimulation could increase intercellular adhesion molecule-1 (ICAM-1) expression in HCAECs. Since anti-inflammatory cytokine interleukin (IL)-37 exhibits intra- and extracellular properties for suppressing innate inflammation, we want to investigate whether IL-37 suppresses ICAM-1 expression and this effect is in parallel with the inhibition of nuclear factor kappa B (NF-κB) activation upon PGN stimulation in HCAECs.
  
  
  METHODS
  HCAECs were treated with IL-37-transfection plasmid or silent mRNA or nothing for 24h, and we test IL-37 expression by immunoblotting. Same treatments prior to PGN stimulation (10μg/ml), we analyzed the expression of ICAM-1 and NF-κB mRNA at 0, 30min, 1 and 2h by real-time PCR. ICAM-1 protein at 24h and NF-κB activation at 0-2h were measured by immunoblotting.
  
  
  RESULTS
  IL-37 and silent IL-37 transfection change the expression of IL-37 protein. Stimulation of PGN increased both NF-κB activation and ICAM-1 expression at mRNA and protein level, but these inflammatory cytokines' expression was significantly decreased in IL-37-transfection cells. Interestingly, both NF-κB activation and ICAM-1 expression were significantly increased when IL-37 was silent.
  
  
  CONCLUSIONS
  As an anti-inflammatory cytokine, IL-37 could decrease both NF-κB and ICAM-1 expression upon TLR2 activation in HCAECs. The suppressed effect of IL-37 on ICAM-1 may be due to its inhibition on NF-κB.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong province, China.
authors.forename: Yandan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong province, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Plastic Surgeon, First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong province, China. Electronic address: caixiangna@126.com.
authors.forename: Xiangna
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong province, China. Electronic address: lijilin@126.com.
authors.forename: Jilin
authors.initials: J
authors.lastname: Li
mesh_terms: D050197:Atherosclerosis / Q000276:immunology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D042783:Endothelial Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010457:Peptidoglycan / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: C508587:IL37 protein, human; D007375:Interleukin-1; D016328:NF-kappa B; D010457:Peptidoglycan; D034741:RNA, Small Interfering; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D018799:Intercellular Adhesion Molecule-1
keywords: HCAECs; ICAM-1; Interleukin-37; NF-κB; TLR2