title: Elastin-derived peptides induce a T-helper type 1 polarization of human blood lymphocytes.
abstract: OBJECTIVE
  Increased level of elastin-derived peptides (EDPs) is observed in the serum of patients with manifestations of arterial diseases. We here investigated whether EDPs might exert, at systemic level, a regulatory role for the T-helper type 1 (Th-1)/Th-2 cellular immune response by human peripheral blood lymphocytes (PBLs) expressing the spliced-galactosidase (S-gal)-elastin receptor.
  
  
  RESULTS
  Using flow cytometry and Western blot analysis, we demonstrated that EDPs led to an activation of the S-gal-elastin receptor associated with cytokine production on PBLs and CD4+ T cell subpopulations. The constitutive expression of the S-gal-elastin receptor at the surface of human PBLs was upregulated at the mRNA (RT-PCR) and protein (ELISA) levels on cell activation. In nonactivated and phytohemagglutinin-activated conditions, expressions of the predominant Th-2 cytokine interleukin-5 (IL-5) and IL-10 were reduced, whereas those of the major Th-1 cytokines interferon-gamma and IL-2 were enhanced by EDPs. Furthermore, we evidenced that EDPs could not only potentiate the IL-12-induced Th-1 profile but also could reverse the Th-2 (over Th-1) profile induced by IL-4. Finally, Th-1 cytokine upregulation was associated to an increased activator protein-1 DNA binding and enhanced pro-matrix metalloproteinase-9 secretion.
  
  
  CONCLUSIONS
  This study highlights the importance of EDPs as stimuli for Th-1 differentiation, whether T cells are in an inactivated state or already orientated toward a Th-1 (IL-12) or Th-2 (IL-4) response.
authors.affiliation: Laboratoire d'Immunologie, Virologie et Bactériologie, Reims, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Debret
authors.forename: Frank
authors.initials: F
authors.lastname: Antonicelli
authors.forename: Aurore
authors.initials: A
authors.lastname: Theill
authors.forename: William
authors.initials: W
authors.lastname: Hornebeck
authors.forename: Philippe
authors.initials: P
authors.lastname: Bernard
authors.forename: Moncef
authors.initials: M
authors.lastname: Guenounou
authors.forename: Richard
authors.initials: R
authors.lastname: Le Naour
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004549:Elastin / Q000378:metabolism*; D005697:Galactosides / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014468:Umbelliferones / Q000378:metabolism
chemical_list: D016207:Cytokines; D005697:Galactosides; D010455:Peptides; D011956:Receptors, Cell Surface; D018808:Transcription Factor AP-1; D014468:Umbelliferones; C101993:cyclohexenoesculetin-beta-galactoside; C054901:elastin-binding proteins; D004549:Elastin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9