Identification of genes and proteins specifically regulated by costimulation of mast cell Fcε Receptor I and chemokine receptor 1.

Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Experimental and Molecular Pathology (Impact Factor: 2.88). 03/2012; 92(3):267-74. DOI: 10.1016/j.yexmp.2012.02.002
Source: PubMed

ABSTRACT Mast cell function is a critical component of allergic reactions. Mast cell responses mediated by the high-affinity immunoglobulin E receptor FcεRI can be enhanced by co-activation of additional receptors such as CC chemokine receptor 1 (CCR1). To examine the downstream effects of FcεRI-CCR1 costimulation, rat basophilic leukemia cells stably transfected with CCR1 (RBL-CCR1 cells) were sensitized and activated with antigen and/or the CCR1 ligand CC chemokine ligand (CCL) 3. Gene and protein expression were determined at 3h and 24h post-activation, respectively, using GeneChip and Luminex bead assays. Gene microarray analysis demonstrated that 32 genes were differentially regulated in response to costimulation, as opposed to stimulation with antigen or CCL3 alone. The genes most significantly up-regulated by FcεRI-CCR1 costimulation were Ccl7, Rgs1, Emp1 and RT1-S3. CCL7 protein was also expressed at higher levels 24h after dual receptor activation, although RGS1, EMP1 and RT1-S3 were not. Of the panel of chemokines and cytokines tested, only CCL2, CCL7 and interleukin (IL)-6 were expressed at higher levels following costimulation. IL-6 expression was seen only after FcεRI-CCR1 costimulation, although the amount expressed was very low. CCL7, CCL2 and IL-6 might play roles in mast cell regulation of late-phase allergic responses.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The prevalence of allergy is rising globally at a very significant rate, which is currently at 20-40% of individuals in westernized nations. In the eye, allergic conditions can take on the acute form such as in seasonal and perennial allergic conjunctivitis, or a more severe and debilitating chronic form such as in vernal and atopic keratoconjunctivitis. Indeed, some key aspects of allergic eye disease pathophysiology are understood, such as the role of mast cells in the acute allergic reaction, and the contribution of eosinophils in late-onset and chronic allergy. However, recent developments in animal models and clinical studies have uncovered new and important roles for previously underappreciated players, including chemokine receptors on ocular surface dendritic cells such as CCR7, the contribution of conjunctival epithelium to immunity, histamine and leukotriene receptors on conjunctival goblet cells and a role for mast cells in late-onset manifestations. Furthermore, recent work in animal models has delineated the contribution of IL-4 in the increased incidence of corneal graft rejection in hosts with allergic conjunctivitis. Recent studies such as these mean that conventional paradigms and concepts should be revisited. The aim of this review is to highlight some of the most recent advances and insights on newly appreciated players in the pathogenesis of allergic eye disease.
    Current eye research 01/2013; DOI:10.3109/02713683.2012.747617 · 1.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Successful treatment of allergic eye disease depends on understanding the pathophysiology of ocular allergy. Thus, in this review, recent experimental and clinical research that has provided significant information about the immunopathology of allergic eye disease will be discussed. Recently, role of various cells, cytokines and chemokines has been scrutinized in the immunopathogenesis of ocular allergy. In this respect, current research highlights contribution of special molecules and cells in the development and clinical features of immunoglobulin E (IgE) and T-cell-mediated eye allergies. Recent findings in molecular immunology of ocular allergy, which comprise complex inflammatory conditions of the conjunctiva, have enabled us to better understand the pathophysiology of these diseases and have aided in the potential development of new therapeutic agents.
    Current Opinion in Allergy and Clinical Immunology 08/2012; 12(5):534-9. DOI:10.1097/ACI.0b013e328357a21b · 3.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mast cells (MC) are major participants in the allergic reaction. In addition they possess immunomodulatory roles in the innate and adaptive immune reactions. Their functions are modulated through a number of activating and inhibitory receptors expressed on their surface. This review deals with some of the most recently described receptors, their expression patterns, ligand(s), signal transduction mechanisms, possible cross-talk with other receptors and, last but not least, regulatory functions that the MC can perform based on their receptor expression in health or in disease. Where the receptor role on MC is still not clear, evidences from other hematopoietic cells expressing them is provided as a possible insight for their function on MC. Suggested strategies to modulate these receptors' activity for the purpose of therapeutic intervention are also discussed.
    Frontiers in Immunology 01/2012; 3:238. DOI:10.3389/fimmu.2012.00238