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      Expression and function of histamine and its receptors in atopic dermatitis

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          Abstract

          Background

          Atopic dermatitis constitutes a most burdensome chronic inflammatory skin disease. Standard treatment is cumbersome and often targets its main symptom, pruritus, only insufficiently.

          Findings

          Recent advances in our understanding of the role of histamine and its four receptors suggest new approaches which target the histamine receptors alone or as combination therapies to more efficiently combat pruritus and inflammation in atopic dermatitis.

          Conclusions

          With this review, we provide an overview on histamine and the expression of its four receptors on skin resident and nonresident cells. Furthermore, we summarize recent studies which suggest anti-histamine therapy to efficiently combat pruritus and inflammation in atopic dermatitis and discuss possible approaches to incorporate these findings into more effective treatment strategies for atopic dermatitis in childhood.

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          Most cited references116

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          A subpopulation of nociceptors specifically linked to itch

          Itch-specific neurons have been sought for decades. The existence of such neurons is in doubt recently due to the observation that itch-mediating neurons also respond to painful stimuli. Here, we genetically labeled and manipulated MrgprA3+ neurons in dorsal root ganglion (DRG) and found that they exclusively innervate the epidermis of the skin and respond to multiple pruritogens. Ablation of MrgprA3+ neurons led to significant reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions whereas pain sensitivity remained intact. Importantly, mice with TRPV1 exclusively expressed in MrgprA3+ neurons exhibited only itch- and not pain behavior in response to capsaicin. Although MrgprA3+ neurons are sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies.
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            Possible pathogenic role of Th17 cells for atopic dermatitis.

            The critical role of IL-17 has recently been reported in a variety of conditions. Since IL-17 deeply participates in the pathogenesis of psoriasis and keratinocyte production of certain cytokines, the involvement of T helper cell 17 (Th17) in atopic dermatitis (AD) is an issue to be elucidated. To evaluate the participation of Th17 cells in AD, we successfully detected circulating lymphocytes intracellularly positive for IL-17 by flow cytometry, and the IL-17+ cell population was found exclusively in CD3+CD4+ T cells. The percentage of Th17 cells was increased in peripheral blood of AD patients and associated with severity of AD. There was a significant correlation between the percentages of IL-17+ and IFN-gamma+ cells, although percentage of Th17 cells was not closely related to Th1/Th2 balance. Immunohistochemically, IL-17+ cells infiltrated in the papillary dermis of atopic eczema more markedly in the acute than chronic lesions. Finally, IL-17 stimulated keratinocytes to produce GM-CSF, TNF-alpha, IL-8, CXCL10, and VEGF. A marked synergistic effect between IL-17 and IL-22 was observed on IL-8 production. The number of Th17 cells is increased in the peripheral blood and acute lesional skin of AD. Th17 cells may exaggerate atopic eczema.
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              Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor.

              Although histaminergic neurones have not yet been histochemically visualized, there is little doubt that histamine (HA) has a neurotransmitter role in the invertebrate and mammalian central nervous system. For example, a combination of biochemical, electrophysiological and lesion studies in rats have shown that histamine is synthesized in and released from a discrete set of neurones ascending through the lateral hypothalamic area and widely projecting in the telencephalon. Histamine acts on target cells in mammalian brain via stimulation of two classes of receptor (H1 and H2) previously characterized in peripheral organs and probably uses Ca2+ and cyclic AMP, respectively, as second messengers. It is well established that several neurotransmitters affect neuronal activity in the central nervous system through stimulation not only of postsynaptic receptors, but also of receptors located presynaptically which often display distinct pharmacological specificity and by which they may control their own release. Such 'autoreceptors' have been demonstrated (or postulated) in the case of noradrenaline, dopamine, serotonin, acetylcholine and gamma-aminobutyric acid (GABA) neurones but have never been demonstrated for histamine. We show here that histamine inhibits its own release from depolarized slices of rat cerebral cortex, an action apparently mediated by a class of receptor (H3) pharmacologically distinct from those previously characterized, that is, the H1 and H2 receptors.
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                Author and article information

                Contributors
                Albrecht.Melanie@mh-hannover.de
                Dittrich.Anna-Maria@mh-hannover.de
                Journal
                Mol Cell Pediatr
                Mol Cell Pediatr
                Molecular and Cellular Pediatrics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                2194-7791
                21 December 2015
                21 December 2015
                December 2015
                : 2
                : 16
                Affiliations
                Department for Pediatric Pneumology, Allergology and Neonatology, Hannover School of Medicine, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
                Article
                27
                10.1186/s40348-015-0027-1
                4686460
                26690068
                e518eaff-8558-4352-8b92-2615cf42389e
                © Albrecht and Dittrich. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 20 June 2015
                : 10 December 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: GRK1441
                Award Recipient :
                Categories
                Mini Review
                Custom metadata
                © The Author(s) 2015

                atopic dermatitis,histamine,histamine receptors,immunology,treatment

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