Skip to main content
Article thumbnail
Location of Repository

Impact of Anti-Inflammatory Agents on the Gene Expression Profile of Stimulated Human Neutrophils: Unraveling Endogenous Resolution Pathways

By Mireille St-Onge, Aline Dumas, Annick Michaud, Cynthia Laflamme, Andrée-Anne Dussault and Marc Pouliot

Abstract

Adenosine, prostaglandin E2, or increased intracellular cyclic AMP concentration each elicit potent anti-inflammatory events in human neutrophils by inhibiting functions such as phagocytosis, superoxide production, adhesion and cytokine release. However, the endogenous molecular pathways mediating these actions are poorly understood. In the present study, we examined their impact on the gene expression profile of stimulated neutrophils. Purified blood neutrophils from healthy donors were stimulated with a cocktail of inflammatory agonists in the presence of at least one of the following anti-inflammatory agents: adenosine A2A receptor agonist CGS 21680, prostaglandin E2, cyclic-AMP-elevating compounds forskolin and RO 20-1724. Total RNA was analyzed using gene chips and real-time PCR. Genes encoding transcription factors, enzymes and regulatory proteins, as well as secreted cytokines/chemokines showed differential expression. We identified 15 genes for which the anti-inflammatory agents altered mRNA levels. The agents affected the expression profile in remarkably similar fashion, suggesting a central mechanism limiting cell activation. We have identified a set of genes that may be part of important resolution pathways that interfere with cell activation. Identification of these pathways will improve understanding of the capacity of tissues to terminate inflammatory responses and contribute to the development of therapeutic strategies based on endogenous resolution

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2654409
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (2008). A2A adenosine receptor and its modulators: overview on a druggable GPCR and on structure-activity relationship analysis and binding requirements of agonists and antagonists.
    2. (2008). A2A receptors in inflammation and injury: lessons learned from transgenic animals.
    3. (1996). Adenosine A2 receptor-induced inhibition of leukotriene B4 synthesis in whole blood ex vivo.
    4. (1996). Adenosine A2-receptor activation inhibits neutrophil-mediated injury to coronary endothelium.
    5. (1994). Adenosine modulation of primed human neutrophils.
    6. (2000). Adenosine receptor occupancy suppresses chemoattractant-induced phospholipase D activity by diminishing membrane recruitment of small GTPases.
    7. (2007). Adenosine Receptors: Therapeutic Aspects for inflammatory and Immune Disease.
    8. (2002). Adenosine upregulates cyclooxygenase-2 in human granulocytes: impact on the balance of eicosanoid generation.
    9. (2000). Adenosine, a potent natural suppressor of arachidonicacidrelease andleukotriene biosynthesis in human neutrophils.
    10. (1983). Adenosine: a physiological modulator of superoxide anion generation by human neutrophils.
    11. (1999). Adenosine. An endogenous inhibitor of arachidonic acid release and leukotriene biosynthesis in human neutrophils.
    12. (2000). Apparent involvement of the A(2A) subtype adenosine receptor in the anti-inflammatory interactions of CGS 21680, cyclopentyladenosine, and IB-MECA with human neutrophils.
    13. (1994). Biochemistry and physiology of the neutrophil.
    14. (2007). Future therapeutic treatment of COPD: struggle between oxidants and cytokines.
    15. (2006). Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils.
    16. (1985). Noncaseating pulmonary granulomas associated with small cell carcinoma of the lung.
    17. (2007). Phenotypic and Functional Changes of Neutrophils Activated by Recently Identified Modulators. Research Signpost.
    18. (1995). Phorbol ester-stimulated adherence of neutrophils to endothelial cells is reduced by adenosine A2 receptor agonists.
    19. (1989). Polymorphonuclear neutrophils: an effective antimicrobial force.
    20. (2003). Possible targeting of G protein coupled receptors to manipulate inflammation in vivo using synthetic and natural ligands.
    21. (2005). Potentiation of Neutrophil Cyclooxygenase-2 by Adenosine: An Early AntiInflammatory Signal.
    22. (2001). Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage.
    23. (1997). Suppression of leukotriene B4 biosynthesis by endogenous adenosine in ligand-activated human neutrophils.
    24. (1993). The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.