Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Konkret geht es um den Diabetes-Patienten mit kardiovaskulären Erkrankungen oder Risiken, die Herzinsuffizienz sowie die kardiovaskuläre Primär- und Sekundärprävention. Sind Sie hier schon auf dem neuesten Stand? Unsere Experten beleuchten, wo und warum das bisherige Procedere geändert werden soll und was in der Praxis sinnvoll ist. Holen Sie sich Ihr Update und 2 CME-Punkte beim MMW-Webinar am 24. April von 17.30 bis 19 Uhr. 
Erweiterte Suche
Anmelden
nach oben
Current Allergy and Asthma Reports
Erschienen in: Current Allergy and Asthma Reports 1/2011

01.02.2011

The Role of the Histamine H4 Receptor in Atopic Dermatitis

verfasst von: Susanne Mommert, Maria Gschwandtner, Ralf Gutzmer, Thomas Werfel

Erschienen in: Current Allergy and Asthma Reports | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

The pathology of atopic dermatitis is orchestrated on the cellular level by several different cell types in the characteristic skin lesions. In such lesions, histamine as a mediator of many biological functions is also present in high concentrations. Most of the cells involved in the inflammatory responses express the histamine H1 and H2 receptors, but drugs targeting these receptors are not clinically effective. The discovery of the fourth histamine receptor, which is differentially expressed on immune and nonimmune cells, has shed new light on the actions of histamine in the complexity of atopic dermatitis. In this review, we describe a possible genetic impact on the expression level of the histamine H4 receptor and summarize the current data regarding the activity of the histamine H4 receptor on the key effector cells in atopic dermatitis. We do so in the context of whether the histamine H4 receptor offers a novel target for effective treatments of inflammatory skin diseases.
Literatur
1.
Leung DY, Boguniewicz M, Howell MD, et al.: New insights into atopic dermatitis. J Clin Invest 2004, 113:651–657.PubMed
2.
Werfel T: The role of leukocytes, keratinocytes, and allergen-specific IgE in the development of atopic dermatitis. J Invest Dermatol 2009, 129:1878–1891.CrossRefPubMed
3.
Stander S, Steinhoff M: Pathophysiology of pruritus in atopic dermatitis: an overview. Exp Dermatol 2002, 11:12–24.CrossRefPubMed
4.
Akdis CA, Akdis M, Bieber T, et al.: Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. Allergy 2006, 61:969–987.CrossRefPubMed
5.
Zampeli E,Tiligada E: The role of histamine H4 receptor in immune and inflammatory disorders. Br.J Pharmacol. 2009; 157:24–33.
6.
• Tiligada E, Zampeli E, Sander K, et al.: Histamine H3 and H4 receptors as novel drug targets. Expert Opin Investig Drugs 2009, 18:1519–1531. The H3R and H4R provide promising and exploitable new drug targets to treat allergy, inflammation, autoimmune disorders, and possibly cancer. CrossRefPubMed
7.
Nakamura T, Itadani H, Hidaka Y, et al.: Molecular cloning and characterization of a new human histamine receptor, HH4R. Biochem Biophys Res Commun 2000, 279:615–620.CrossRefPubMed
8.
Oda T, Morikawa N, Saito Y, et al.: Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. J Biol Chem 2000, 275:36781–36786.CrossRefPubMed
9.
Huang JF, Thurmond RL: The new biology of histamine receptors. Curr Allergy Asthma Rep 2008, 8:21–27.CrossRefPubMed
10.
Pallinger E, Csaba G: Presence and distribution of biogenic amines (histamine, serotonin and epinephrine) in immunophenotyped human immune cells. Inflamm Res 2008, 57:530–534.CrossRefPubMed
11.
Thurmond RL, Gelfand EW, Dunford PJ.: The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 2008, 7:41–53.CrossRefPubMed
12.
• Gutzmer R, Mommert S, Gschwandtner M, et al.: The histamine H4 receptor is functionally expressed on T(H)2 cells. J Allergy Clin Immunol 2009, 123:619–625. H4R stimulation induces AP-1 and upregulates the production of IL-31 mRNA. This study provides a new link between histamine and pruritus. CrossRefPubMed
13.
Dijkstra D, Stark H, Chazot PL, et al.: Human inflammatory dendritic epidermal cells express a functional histamine H4 receptor. J Invest Dermatol 2008, 128:1696–1703.CrossRefPubMed
14.
Dijkstra D, Leurs R, Chazot P, et al.: Histamine downregulates monocyte CCL2 production through the histamine H4 receptor. J Allergy Clin Immunol 2007, 120:300–307.CrossRefPubMed
15.
Heinzmann A, Deichmann KA: Genes for atopy and asthma. Curr Opin Allergy Clin Immunol 2001, 1:387–392.PubMed
16.
•• Yu B, Shao Y, Zhang J, et al.: Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis. Br J Dermatol 2010, 162:1038–1043. SNPs within the H4R gene were found to be significantly associated with AD. CrossRefPubMed
17.
Yu B, Shao Y, Li P, et al.: Copy number variations of human histamine H4 receptor gene are associated with systemic lupus erythematosus. Br J Dermatol 2010 Jul 2 (Epub ahead of print).
18.
van Rijn RM, van Marle A, Chazot PL, et al.: Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor. Biochem J 2008, 414:121–131.CrossRefPubMed
19.
Buckland KF, Williams TJ, Conroy DM: Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor. Br J Pharmacol 2003, 140:1117–1127.CrossRefPubMed
20.
Ling P, Ngo K, Nguyen S, et al.: Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol 2004, 142:161–171.CrossRefPubMed
21.
Hofstra CL, Desai PJ, Thurmond RL, et al.: Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. J Pharmacol Exp Ther 2003, 305:1212–1221.CrossRefPubMed
22.
Novak N, Bieber T, Leung DY: Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol 2003, 112:S128–39.CrossRefPubMed
23.
Spergel JM, Mizoguchi E, Oettgen H, et al.: Roles of Th1 and Th2 cytokines in a murine model of allergic dermatitis. J Clin Invest 1999, 103:1103–1111.CrossRefPubMed
24.
Raap U, Wichmann K, Bruder M, et al.: Correlation of IL-31 serum levels with severity of atopic dermatitis. J Allergy Clin Immunol 2008, 122:421–423.CrossRefPubMed
25.
Kasraie S, Niebuhr M, Werfel T: Interleukin (IL)-31 induces pro-inflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins. Allergy 2010, 65:712–721.CrossRefPubMed
26.
• Cowden JM, Zhang M, Dunford PJ, et al.: The histamine H(4) receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. J Invest Dermatol 2010, 130:1023–1033. H4R antagonists exert effective antipruritic and anti-inflammatory functions in a murine skin model that mimics several features of AD. CrossRefPubMed
27.
• Rossbach K, Wendorff S, Sander K, et al.: Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation. Exp Dermatol 2009, 18:57–63. The H4R antagonist JNJ 7777120 reduced scratching behavior in two different murine models of allergic contact dermatitis but failed to reduce the allergic inflammatory response. CrossRefPubMed
28.
Horr B, Borck H, Thurmond R, et al.: STAT1 phosphorylation and cleavage is regulated by the histamine (H4) receptor in human atopic and non-atopic lymphocytes. Int Immunopharmacol 2006, 6:1577–1585.CrossRefPubMed
29.
Sugata Y, Okano M, Fujiwara T, et al.: Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T-cell responses. Immunology 2007, 121:266–275.CrossRefPubMed
30.
Koga C, Kabashima K, Shiraishi N, et al.: Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol 2008, 128:2625–2630.CrossRefPubMed
31.
Toda M, Leung DY, Molet S, et al.: Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol 2003, 111:875–881.CrossRefPubMed
32.
Mommert S, Koether B, Gschwandtner M, et al.: Human memory Th17 cells express a functional H4 receptor. Presented at the European Histamine Research Society XXXIX Meeting, Durham, UK; July 12–16, 2010.
33.
Ou LS, Goleva E, Hall C, et al.: T regulatory cells in atopic dermatitis and subversion of their activity by superantigens. J Allergy Clin Immunol 2004, 113:756–763.CrossRefPubMed
34.
Schnopp C, Rad R, Weidinger A, et al.: Fox-P3-positive regulatory T cells are present in the skin of generalized atopic eczema patients and are not particularly affected by medium-dose UVA1 therapy. Photodermatol Photoimmunol Photomed 2007, 23:81–85.CrossRefPubMed
35.
Morgan RK, McAllister B, Cross L, et al.: Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and inhibits allergic asthma in a murine model. J Immunol 2007, 178:8081–8089.PubMed
36.
Neumann D, Beermann S, Seifert R: Does the histamine H4 receptor have a pro- or anti-inflammatory role in mouse bronchial asthma? Pharmacology 2010, 85:217–223.CrossRefPubMed
37.
Deml KF, Beermann S, Neumann D, et al.: Interactions of histamine H1 receptor agonists and antagonists with the human histamine H4 receptor. Mol Pharmacol 2009, 76: 1019–1030.CrossRefPubMed
38.
Kronenberg M, Gapin L,: The unconventional lifestyle of NKT cells. Nat Rev Immunol 2002, 2:557–568.PubMed
39.
• Simon D, Kozlowski E, Simon H.: Natural killer T cells expressing IFN-gamma and IL-4 in lesional skin of atopic eczema. Allergy 2009, 64:1681–1684. NK T cells expressing IFN-γ and IL-4 were detected by immunofluorescence staining among infiltrating T lymphocytes in lesions of atopic eczema and other eczematous skin diseases. CrossRefPubMed
40.
.• Leite-de-Moraes MC, Diem S, Michel ML, et al.: Cutting edge: histamine receptor H4 activation positively regulates in vivo IL-4 and IFN-gamma production by invariant NKT cells. J Immunol 2009, 182:1233–1236. Studies in histamine-free (histidine decarboxylase–deficient) and H4R-deficient mice provide evidence that histamine influences IL-4 and IFN-γ production in iNKT cells via the H4R. PubMed
41.
Buentke E, Heffler LC, Wilson JL, et al.: Natural killer and dendritic cell contact in lesional atopic dermatitis skin--Malassezia-influenced cell interaction. J Invest Dermatol 2002, 119:850–857.CrossRefPubMed
42.
Damaj BB, Becerra CB, Esber HJ, et al.: Functional expression of H4 histamine receptor in human natural killer cells, monocytes, and dendritic cells. J Immunol 2007, 179:7907–7915.PubMed
43.
Gutzmer R, Koether B, Gschwandtner M, et al.: Histamine downregulates IL-27, another member of the IL-12 family, via H2R and H4R on human monocytes. Presented at the European Histamine Research Society XXXIX Meeting, Durham, UK; July 12–16, 2010.
44.
Wittmann M, Zeitvogel J, Wang D, et al.: IL-27 is expressed in chronic human eczematous skin lesions and stimulates human keratinocytes. J Allergy Clin Immunol 2009, 124:81–89.CrossRefPubMed
45.
Gutzmer R, Diestel C, Mommert S, et al.: Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. J Immunol 2005, 174:5224–5232.PubMed
46.
Baumer W, Wendorff S, Gutzmer R, et al.: Histamine H4 receptors modulate dendritic cell migration through skin--immunomodulatory role of histamine. Allergy 2008, 63:1387–1394.CrossRefPubMed
47.
Gschwandtner M, Schakel K, Werfel T, et al.: Histamine H(4) receptor activation on human slan-dendritic cells down-regulates their pro-inflammatory capacity. Immunology 2010 Aug 16 (Epub ahead of print).
48.
• Gschwandtner M, Rossbach K, Dijkstra D, et al.: Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and function. Allergy 2010, 65:840–849. The H4R is expressed on primary LCs from human and murine skin samples. On human LCs, H4R stimulation suppresses CCL2 and mediates chemotaxis. CrossRefPubMed
49.
Wittmann M, Werfel T: Interaction of keratinocytes with infiltrating lymphocytes in allergic eczematous skin diseases. Curr Opin Allergy Clin Immunol 2006, 6:329–334.CrossRefPubMed
50.
• Yamaura K, Oda M, Suwa E, et al.: Expression of histamine H4 receptor in human epidermal tissues and attenuation of experimental pruritus using H4 receptor antagonist. J Toxicol Sci 2009; 34:427–431. Immunofluorescence staining revealed a greater expression of the H4R in the epidermal upper layer compared with the lower layer. The histamine receptor antagonist JNJ 7777120 significantly reduced histamine- and substance P–induced scratching behavior in mice. CrossRefPubMed
Metadaten
Titel
The Role of the Histamine H4 Receptor in Atopic Dermatitis
verfasst von
Susanne Mommert
Maria Gschwandtner
Ralf Gutzmer
Thomas Werfel
Publikationsdatum
01.02.2011
Verlag
Current Science Inc.
Erschienen in
Current Allergy and Asthma Reports / Ausgabe 1/2011
Print ISSN: 1529-7322
Elektronische ISSN: 1534-6315
DOI
https://doi.org/10.1007/s11882-010-0162-7

Weitere Artikel der Ausgabe 1/2011

Current Allergy and Asthma Reports 1/2011 Zur Ausgabe

ReviewPaper

Perspectives on Anaphylaxis Epidemiology in the United States with New Data and Analyses

ReviewPaper

Diagnosis of Allergy and Asthma in Childhood

ReviewPaper

The Impact of Vitamin D on Regulatory T Cells

ReviewPaper

Exercise-Induced Anaphylaxis: An Update on Diagnosis and Treatment

Clinical Trial Report

The Role of Vitamin D in Asthmatic Children

ReviewPaper

Innate Signaling in Otitis Media: Pathogenesis and Recovery

Neu im Fachgebiet HNO

16.04.2024 | HNO-Chirurgie | Nachrichten

HNO-Op. auch mit über 90?

16.04.2024 | Tonsillektomie | Nachrichten

Intrakapsuläre Tonsillektomie gewinnt an Boden

15.04.2024 | Hörsturz | Nachrichten

Bilateraler Hörsturz hat eine schlechte Prognose

08.04.2024 | Larynxpapillomatose | Nachrichten

RRP: Adjuvante HPV-Impfung in jedem Alter empfehlenswert
weitere anzeigen

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen