Immunomodulatory mast cells: Negative, as well as positive, regulators of immunity

Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA.
Nature Reviews Immunology (Impact Factor: 33.84). 07/2008; 8(6):478-86. DOI: 10.1038/nri2327
Source: PubMed

ABSTRACT Mast cells can promote inflammation and other tissue changes in IgE-associated allergic disorders, as well as in certain innate and adaptive immune responses that are thought to be independent of IgE. However, mast cells can also have anti-inflammatory and immunosuppressive functions. Here, we review the evidence that mast cells can have negative, as well as positive, immunomodulatory roles in vivo, and we propose that mast cells can both enhance and later suppress certain features of an immune response.

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    • "Inflammation is a natural host defense response to invading pathogens and tissue injury with the involvement of phagocytic cells such as macrophages, mast cells, dendritic cells, granulocytes and the innate lymphocytes (Galli et al., 2008). In many instances, inflammation is demonstrated to be an important contributor to diseases such as cancer, diabetes and cardiovascular disease. "
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    ABSTRACT: The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana. The in silico analysis of inflammatory mediators such as cyclooxygenase (COX) and nuclear factor-kappa B (NF-kB) were performed via molecular docking. Further evaluation of anti-inflammatory effect was conducted in lipopolysaccharide (LPS) induced RAW264.7 macrophages. Suppression of activated NF-kB was analyzed by high content screening. βM triggered inhibition of COX-1 and COX-2 in vitro were studied using biochemical kit. The in vivo model used in this study was carrageenan-induced peritonitis model, where reduction in carrageenan-induced peritonitis is measured by leukocyte migration and vascular permeability. In addition, the evaluation of βM's effect on carrageenan induced TNF-α and IL-1β release on peritoneal fluid was also carried out. Treatment with βM could inhibit the LPS-induced NO production but not the viability of RAW264.7. Similarly, βM inhibited PGE2 production and the cytokines: TNF-α and IL-6. The COX catalysed prostaglandin biosynthesis assay had showed selective COX-2 inhibition with a 53.0±6.01% inhibition at 20µg/ml. Apart from this, βM was capable in repressing translocation of NF-kB into the nucleus. These results were concurrent with molecular docking which revealed COX-2 selectivity and NF-kB inhibition. The in vivo analysis showed that after four hours of peritonitis, βM was unable to reduce vascular permeability, yet could decrease the total leukocyte migration; particularly, neutrophils. Meanwhile, dexamethasone 0.5mg/kg, successfully reduced vascular permeability. The levels of TNF-α and IL-1β in peritoneal fluid was reduced significantly by βM treatment. The current study supports the traditional use of Garcinia mangostana fruit hull for treatment of inflammatory conditions. In addition, it is clear that the anti-inflammatory efficacy of this plant is not limited to the presence of α and ɣ, but β also with significant activity.
    Journal of ethnopharmacology 03/2014; 153(2). DOI:10.1016/j.jep.2014.02.051 · 2.94 Impact Factor
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    • "Mast cells are innate immune cells; in response to antigen challenge, they release proinflammatory mediators that potentiates effector cell recruitment and complements other components of the immune system to enhance the inflammatory response (Mekori and Metcalfe, 1999; Galli et al., 2008). Mast cells also have an anti-inflammatory function (Galli et al., 2008). Other effects of mucosal mast cell deficiency in W-sh/W-sh mice are, increase in permeability of intestinal segments by increased crypt depth, decrease in migration of epithelial cells and down regulation of expression of the tight junction protein claudin-3 (Groschwitz et al., 2009). "
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    ABSTRACT: The initial hypothesis suggested that the interstitial cells of Cajal (ICC) played an essential role in mediating enteric neuronal input to smooth muscle cells. Much information for this hypothesis came from studies in W/W(v) mice lacking ICC. However, mast cells, which play critical roles in regulating inflammation in their microenvironment, are also absent in W/W(v) mice. We tested the hypothesis that the depletion of mast cells in W/W(v) mice generates inflammation in fundus muscularis externa (ME) that impairs smooth muscle reactivity to Ach, independent of the depletion of ICC. We performed experiments on the fundus ME from wild type (WT) and W/W(v) mice before and after reconstitution of mast cells by bone marrow transplant. We found that mast cell deficiency in W/W(v) mice significantly increased COX-2 and iNOS expression and decreased smooth muscle reactivity to Ach. Mast cell reconstitution or concurrent blockade of COX-2 and iNOS restored smooth muscle contractility without affecting the suppression of c-kit in W/W(v) mice. The expression of nNOS and ChAT were suppressed in W/W(v) mice; mast cell reconstitution did not restore them. We conclude that innate inflammation induced by mast cell deficiency in W/W(v) mice impairs smooth muscle contractility independent of ICC deficiency. The impairment of smooth muscle contractility and the suppression of the enzymes regulating the synthesis of Ach and NO in W/W(v) mice need to be considered in evaluating the role of ICC in regulating smooth muscle and enteric neuronal function in W/W(v) mice.
    Frontiers in Physiology 02/2014; 5:22. DOI:10.3389/fphys.2014.00022 · 3.50 Impact Factor
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    • "Upon activation, MCs can produce a broad spectrum of inflammatory cytokines, chemokines, lipid compounds and vasoactive amines, which autoconfer the peculiar capacity to respond to a wide range of external stimuli and drive the immune response (Galli et al., 2008; Gri et al., 2012). The idea that MCs can also translate the immunological effect of AhR activation is extremely new and has been investigated in only 3 papers in the last 2 years. "
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    ABSTRACT: The activation of the transcription factor aryl hydrocarbon receptor (AhR) is modulated by a wide variety of xenobiotics and ligands deriving from products of metabolism. The study of the contribution of AhR to allergic diseases has gained much interest in recent years. Here we discuss the role that environmental factors and metabolic products, particularly acting on AhR-expressing mast cells (MCs), could have in the development of local allergic/atopic response. Thus, this review will cover: a brief overview of the AhR mechanism of action in the immune system; a description of different AhR ligands and their effects to IgE-mediated MC activation in the allergic response, with particular attention to the role of IL-17; a discussion about the potential involvement of AhR in immune tolerance; and a conclusion on human diseases in which direct AhR activation of MC might have a major impact.
    Molecular Immunology 01/2014; 63(1). DOI:10.1016/j.molimm.2014.02.015 · 3.00 Impact Factor
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