| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B Down-Regulation1
* Laboratoire d’Immunologie et de Microbiologie, Immuno-Pharmacologie Cellulaire et Moléculaire, EA3796 Unité de Formation et de Recherche de Pharmacie, Reims, France;
Laboratoire de Biochimie et de Dermatologie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6198, Unité de Formation et de Recherche de Médecine, Reims, France; and
Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche Santé 514, Centre Hospitalier Universitaire Maison Blanche, Reims, France
In inflammatory diseases, strong release of elastinolytic proteases results in elastin fiber degradation generating elastin peptides (EPs). Chemotactic activity for inflammatory cells was, among wide range of properties, the former identified biological activity exerted by EPs. Recently, we demonstrated the ability of EPs to favor a Th1 cytokine (IL-2, IFN-
) cell response in lymphocytes and to regulate IL-1
expression in melanoma cells. We hypothesized that EPs might also influence inflammatory cell properties by regulating cytokine expression by these cells. Therefore, we investigated the influence of EPs on inflammatory cytokine synthesis by human monocytes. We evidenced that EPs down-regulated both at the mRNA and protein levels the proinflammatory TNF-
, IL-1, and IL-6 expression in LPS-activated monocytes. Such negative feedback loop could be accounted solely for EP-mediated effects on proinflammatory cytokine production because EPs did not affect anti-inflammatory IL-10 or TGF- secretion by LPS-activated monocytes. Furthermore, we demonstrated that EP effect on proinflammatory cytokine expression by LPS-stimulated monocytes could not be due either to a decrease of LPS receptor expression or to an alteration of LPS binding to its receptor. The inhibitory effects of EPs on cytokine expression were found to be mediated by receptor (spliced galactosidase) occupancy, as being suppressed by lactose, and to be associated with the decrease of NF-
B-DNA complex formation. As a whole, these results demonstrated that EP/spliced galactosidase interaction on human monocytes down-regulated NF-B-dependent proinflammatory cytokine expression and pointed out the critical role of EPs in the regulation of inflammatory response.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 T.B. is the recipient of a bursary from the French government (Ministère de l’Education Nationale et de la Recherche).
2 Current address: Institut de Biologie et de Chimie des Protéines, Lyon, France.
3 Address correspondence and reprint requests to Dr. Richard Le Naour, Laboratoire d’Immunologie et de Microbiologie, Immuno-Pharmacologie Cellulaire et Moléculaire, EA3796, IFR53, Unité de Formation et de Recherche de Pharmacie, 1 Rue du Maréchal Juin, 51096 Reims Cedex, France. E-mail address: richard.lenaour{at}univ-reims.fr
4 Abbreviations used in this paper: EP, elastin peptide; ChIP, chromatin immunoprecipitation; EBP, elastin-binding protein; GRO, growth-related oncogene; PKC, protein kinase C; S-gal, spliced galactosidase.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
