title: The glucocorticoid dexamethasone inhibits U937 cell adhesion and neutrophil release via RhoA/ROCK1-dependent and independent pathways.
abstract: OBJECTIVE
  The aim of the present study was to investigate the role of the Ras homolog family member A (RhoA)/Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) signaling pathway in the inhibition of inflammatory responses by the glucocorticoid dexamethasone (Dex).
  
  
  METHODS
  The inhibitory effects of Dex and Rho-kinase inhibitor fasudil (Fas) on phorbol ester-induced release of O2(-) and MPO from neutrophils and on U937 mononuclear cell adhesion were examined along with the expression and activity levels of RhoA and ROCK1.
  
  
  RESULTS
  High doses of Dex rapidly inhibited the release of O2(-) and myeloperoxidase (MPO) from neutrophils and the adhesion of U937 cells, while Fas was only found to inhibit U937 cell adhesion. Additionally, Dex suppressed ROCK1 activity. However, Dex had no effects on ROCK1 or RhoA expression levels or on RhoA activity. Neither the glucocorticoid receptor antagonist mifepristone (RU-486) nor the protein synthesis inhibitor cycloheximide (CHX) was able to suppress the effects of Dex (p>0.05).
  
  
  CONCLUSIONS
  The present findings indicate that Dex suppressed neutrophil release through ROCK1-independent mechanisms and inhibited the adhesion of U937 mononuclear cells through ROCK1-dependent non-genomic mechanisms that did not involve RhoA.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Molecular Biology Center, Research Institute of Field Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Renping
authors.initials: R
authors.lastname: Xiong
authors.forename: Xingyun
authors.initials: X
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yalei
authors.initials: Y
authors.lastname: Ning
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Yuanguo
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020298:U937 Cells; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D047428:Protein Kinase Inhibitors; D013481:Superoxides; C066737:RHOA protein, human; D003907:Dexamethasone; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009195:Peroxidase; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D013755:Tetradecanoylphorbol Acetate; C049347:fasudil