title: Glucocorticoids and IL-10, but not 6-MP, 5-ASA or sulfasalazine block endothelial expression of MAdCAM-1: implications for inflammatory bowel disease therapy.
abstract: BACKGROUND
  Enhanced MAdCAM-1 (mucosal addressin cell adhesion molecule-1) expression is associated with the aetiology of inflammatory bowel disease, but little is known about MAdCAM-1: regulation, or how inflammatory bowel disease therapies modulate MAdCAM-1.
  
  
  OBJECTIVE
  To examine how agents currently used to treat inflammatory bowel disease affect MAdCAM-1: induced by tnf-alpha in an in vitro model of inflammatory bowel disease.
  
  
  METHODS
  Endothelial monolayers were pretreated with dexamethasone (DEX): 5-aminosalicylic acid (5-ASA), 6-mercaptopurine (6-MP), sulfasalazine or interleukin-10: (IL-10: prior to TNF-alpha (20 ng/mL), and MAdCAM-1: measured by Western blotting, RT-PCR, EMSA and lymphocyte adhesion assays.
  
  
  RESULTS
  MAdCAM-1: was induced dose- and time-dependently by TNF-alpha on endothelial cells. Either dexamethasone or IL-10: reduced TNF-alpha-induced MAdCAM-1: protein, mRNA and lymphocyte adhesion. However, neither 5-ASA, sulfasalazine nor 6-MP blocked MAdCAM-1 induction.
  
  
  CONCLUSIONS
  Our data indicate that dexamethasone or IL-10 can exert therapeutic activity in inflammatory bowel disease through MAdCAM-1 inhibition. 5-ASA, sulfasalazine and 6-MP, while beneficial in inflammatory bowel disease, do not directly control MAdCAM-1, and are beneficial through inhibition of other inflammatory processes.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
authors.forename: T
authors.initials: T
authors.lastname: Oshima
authors.forename: K
authors.initials: K
authors.lastname: Pavlick
authors.forename: M B
authors.initials: MB
authors.lastname: Grisham
authors.forename: P
authors.initials: P
authors.lastname: Jordan
authors.forename: K
authors.initials: K
authors.lastname: Manas
authors.forename: T
authors.initials: T
authors.lastname: Joh
authors.forename: M
authors.initials: M
authors.lastname: Itoh
authors.forename: J S
authors.initials: JS
authors.lastname: Alexander
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000209:etiology; D016753:Interleukin-10 / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects; D015122:Mercaptopurine / Q000494:pharmacology*; D019804:Mesalamine / Q000494:pharmacology*; D051379:Mice; D009088:Mucoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012460:Sulfasalazine / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D005938:Glucocorticoids; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D012460:Sulfasalazine; D019804:Mesalamine; D003907:Dexamethasone; D015122:Mercaptopurine; D013937:Thymidine Kinase; C092717:thymidine kinase 1