Published online before print April 28, 2005, doi: 10.1161/01.ATV.0000168412.50855.9f
© 2005 American Heart Association, Inc.
Vascular Biology |
Elastin-Derived Peptides Induce a T-Helper Type 1 Polarization of Human Blood Lymphocytes
From the Laboratoire d’Immunologie Virologie et Bactériologie (R.D., A.T., M.G., R.L.N.), and Laboratoire de Biochimie (R.D., F.A., W.H., P.B.), Reims, France.
Correspondence to Richard Le Naour, PhD, Laboratoire d’Immunologie, Virologie et Bactériologie, IPCM, EA 3796, IFR53, UFR de Pharmacie, 1 rue du Maréchal Juin, 51096 Reims Cedex, France. E-mail richard.lenaour{at}univ-reims.fr
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.
Methods and 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-
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.
Elastin-derived peptides, as generated during arterial diseases such as AAA, were shown to act as potent T-cell stimuli inducing Th-1 polarization and MMP-9 production.
Key Words: elastin peptides • T lymphocytes • cytokines • Th-1/Th-2 • MMP-9 • AP-1
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