title: Sphingosine 1-phosphate receptor 1 (S1PR1) agonist CYM5442 inhibits expression of intracellular adhesion molecule 1 (ICAM1) in endothelial cells infected with influenza A viruses.
abstract: BACKGROUND
  Influenza A virus infection and its complications effect a large population worldwide. Endothelial cells are an important component in lung inflammation caused by influenza A virus infection. The roles of endothelial sphingosine 1-phophate receptor 1 (S1PR1) in the regulation of molecules involved in leukocyte recruitment during influenza A virus infection still remain unknown. In this report, we tested our hypothesis that S1PR1 agonist CYM5442 inhibits expression of intracellular adhesion molecules 1 (ICAM1) in endothelial cells infected with influenza A virus.
  
  
  METHODS
  Human pulmonary microvascular endothelial cells (HPMEC) were infected with influenza A virus H1N1. Expression of cytokines, chemokines, interferons, and cellular adhesion molecules was measured by q-PCR. Expression of ICAM1 was further tested by Western Blotting. A S1PR1 agonist CYM5442 was added to the culture media to assess CYM5442's inhibitory effects during virus infection.
  
  
  RESULTS
  HPMEC could be infected with H1N1 and responded to produce pro-inflammatory cytokines, chemokines, type I interferons, and cellular adhesion molecules. Addition of CYM5442 in culture media reduced the production of ICAM1 via a dosage- and time-dependent manner. CYM5442 inhibited the activation of nuclear factor (NF)-κB. The regulatory effects of CYM5442 were β-arrestin2-dependent.
  
  
  CONCLUSIONS
  Activated S1PR1 signaling regulates the production of cellular adhesion molecules by inhibiting NF- κB activation via a β-arrestin2-dependent manner.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.|Department of Emergency Medicine, the Second Affiliated Hospital, Southeast University, Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Si-Mei
authors.initials: SM
authors.lastname: Shen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Peng-Peng
authors.initials: PP
authors.lastname: Zhang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000821:virology*; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: C532995:2-(4-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl amino)ethanol; D016207:Cytokines; D007189:Indans; D016328:NF-kappa B; D010069:Oxadiazoles; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; D018799:Intercellular Adhesion Molecule-1