title: Inhibition of B7-1 (CD80) by RhuDex® reduces lipopolysaccharide-mediated inflammation in human atherosclerotic lesions.
abstract: BACKGROUND
  Atherosclerosis is based on a chronic inflammatory process including the innate and adaptive immune response. Costimulatory molecules and their receptors provide decisive signals for antigen-specific cell activation. The contribution of B7-related pathways to atherosclerosis has hardly been explored.
  
  
  METHODS
  In the present study, we investigated the contribution of B7-1 to inflammation and tissue injury in the human plaque microenvironment in order to identify possible target structures of future therapeutic agents ex vivo and in vitro.
  
  
  RESULTS
  Carotid artery plaque stimulation with lipopolysaccharides (LPS) could be significantly inhibited by RhuDex(®), a specific inhibitor of the costimulatory molecule B7-1 ex vivo (P<0.001). Coculture of antigen-presenting cells with T-cells demonstrated that the inhibitory effects of RhuDex(®) derived from reduced T-cell activation. In addition, incubation of monocytes/macrophages with LPS and RhuDex(®) resulted in an inhibitory negative feedback on antigen-presenting cells. Signaling pathways affected by RhuDex(®) seem to be nuclear transcription factor kappa B, activator protein-1, and extracellular signal-regulated kinase 1/2.
  
  
  CONCLUSIONS
  The present data support B7-1 alone as an important costimulatory molecule in the context of LPS-mediated inflammation in atherosclerotic lesions. Due to its marked inhibitory effects, RhuDex(®) may be a useful therapy to modulate the inflammatory milieu in atherosclerosis.
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Doesch
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Gleissner
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Akhavanpoor
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Rohde
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: Deniz
authors.initials: D
authors.lastname: Okuyucu
authors.affiliation: Department of Vascular Surgery, University of Heidelberg, Germany.
authors.forename: Maani
authors.initials: M
authors.lastname: Hakimi
authors.affiliation: Department of Cardiology, SLK Hospital Heilbronn, Bad Friedrichshall, Germany.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dengler
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Erbel
mesh_terms: D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology*; D018122:B7-1 Antigen / Q000037:antagonists & inhibitors* / Q000502:physiology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides
keywords: B7; CD86; atherosclerosis; costimulation