title: CD40 and OX40 ligand are increased on stimulated asthmatic airway smooth muscle.
abstract: BACKGROUND
  Severe, persistent asthma is characterized by airway smooth muscle hyperplasia, inflammatory cell infiltration into the smooth muscle, and increased expression of many cytokines, including IL-4, IL-13, IL-1beta, and TNF-alpha. These cytokines have the potential to alter the expression of surface receptors such as CD40 and OX40 ligand on the airway smooth muscle cell.
  
  
  OBJECTIVE
  To examine whether cytokines alter expression of CD40 and OX40 ligand on airway smooth muscle cells and identify any differences in response between asthmatic and nonasthmatic airway smooth muscle cells.
  
  
  METHODS
  We used flow cytometry and immunohistochemistry to detect CD40 and OX40 ligand on airway smooth muscle cells cultured in the presence of TNF-alpha, IL-1beta, IL-4, or IL-13. Prostaglandin E 2 levels were assessed by ELISA.
  
  
  RESULTS
  TNF-alpha increased expression of both CD40 and OX40 ligand on both asthmatic and nonasthmatic airway smooth muscle cells. The level of expression was significantly greater on the asthmatic cells. IL-1beta alone had no effect, but it attenuated the TNF-induced expression of both CD40 and OX40 ligand. The mechanism of inhibition was COX-dependent for CD40 and was COX-independent but cyclic AMP-dependent for OX40 ligand. IL-4 and IL-13 had no effect.
  
  
  CONCLUSIONS
  Our study has demonstrated that TNF-alpha and IL-1beta have the potential to modulate differentially the interactions between cells present in the inflamed airways of a patient with asthma and therefore to contribute to the regulation of airway inflammation and remodeling.
authors.affiliation: Department of Pharmacology, University of Sydney, Sydney, NSW, Australia. janette@pharmacol.usyd.edu.au
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.forename: Anita E
authors.initials: AE
authors.lastname: Blake
authors.forename: Sarah
authors.initials: S
authors.lastname: Boustany
authors.forename: Peter R A
authors.initials: PR
authors.lastname: Johnson
authors.forename: Carol L
authors.initials: CL
authors.lastname: Armour
authors.forename: Judith L
authors.initials: JL
authors.lastname: Black
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Hunt
authors.forename: J Margaret
authors.initials: JM
authors.lastname: Hughes
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D015232:Dinoprostone / Q000502:physiology; D004338:Drug Combinations; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D053278:OX40 Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D004338:Drug Combinations; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053278:OX40 Ligand; C089251:TNFSF4 protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D015232:Dinoprostone