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      The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets

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          Abstract

          Histamine and its receptors (H1R–H4R) play a crucial and significant role in the development of various allergic diseases. Mast cells are multifunctional bone marrow-derived tissue-dwelling cells that are the major producer of histamine in the body. H1R are expressed in many cells, including mast cells, and are involved in Type 1 hypersensitivity reactions. H2R are involved in Th1 lymphocyte cytokine production. H3R are mainly involved in blood–brain barrier function. H4R are highly expressed on mast cells where their stimulation exacerbates histamine and cytokine generation. Both H1R and H4R have important roles in the progression and modulation of histamine-mediated allergic diseases. Antihistamines that target H1R alone are not entirely effective in the treatment of acute pruritus, atopic dermatitis, allergic asthma, and other allergic diseases. However, antagonists that target H4R have shown promising effects in preclinical and clinical studies in the treatment of several allergic diseases. In the present review, we examine the accumulating evidence suggesting novel therapeutic approaches that explore both H1R and H4R as therapeutic targets for histamine-mediated allergic diseases.

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          Most cited references 112

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              The role of mast cells in allergic inflammation.

               Kawa Amin (2012)
              The histochemical characteristics of human basophils and tissue mast cells were described over a century ago by Paul Ehrlich. When mast cells are activated by an allergen that binds to serum IgE attached to their FcɛRI receptors, they release cytokines, eicosanoids and their secretory granules. Mast cells are now thought to exert critical proinflammatory functions, as well as potential immunoregulatory roles, in various immune disorders through the release of mediators such as histamine, leukotrienes, cytokines chemokines, and neutral proteases (chymase and tryptase). The aim of this review is to describe the role of mast cells in allergic inflammation. Mast cells interact directly with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been shown to have inhibitory effects on mast cell degranulation and mediator release. This review shows that mast cells play an active role in such diverse diseases as asthma, rhinitis, middle ear infection, and pulmonary fibrosis. In conclusion, mast cells may not only contribute to the chronic airway inflammatory response, remodeling and symptomatology, but they may also have a central role in the initiation of the allergic immune response, that is providing signals inducing IgE synthesis by B-lymphocytes and inducing Th2 lymphocyte differentiation. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                13 August 2018
                2018
                : 9
                Affiliations
                1Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology , Kattankulathur, Tamil Nadu, India
                2Department of Biochemistry, All India Institute of Medical Sciences , Bhopal, Madhya Pradesh, India
                3Discipline of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI) , Indore, Madhya Pradesh, India
                4Central Food Technological Research Institute-Resource Centre , Lucknow, India
                5Department of Pharmaceutical and Administrative Sciences, Western New England University , Springfield, MA, United States
                6Department of Dermatology and Allergy, Charité – Universitätsmedizin Berlin , Berlin, Germany
                7Department of Biotechnology, Government of India , New Delhi, India
                Author notes

                Edited by: Carlo Pucillo, Università degli Studi di Udine, Italy

                Reviewed by: Axel Lorentz, University of Hohenheim, Germany; Meenu Sharma, University of Texas MD Anderson Cancer Center, United States

                Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.01873
                6099187
                Copyright © 2018 Thangam, Jemima, Singh, Baig, Khan, Mathias, Church and Saluja.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 116, Pages: 9, Words: 7087
                Categories
                Immunology
                Mini Review

                Immunology

                histamine, histamine receptors, mast cells, allergy, inflammation, antihistamines

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