2672
Views & Citations1672
Likes & Shares
It became
apparent that histamine exacerbates allergic dermatitis through experiment with
histamine-deficient mice. Histamine induces infiltration of inflammatory cells
and epidermal hyperplasia in chronic allergic dermatitis. Histamine also
induces itchy sensation as well as other pruritogens in allergic dermatitis.
Many kinds of cells in the skin express histamine receptors and allergic
responses are induced through histamine H 1-4 receptors, especially H1 and H4
receptors.
Keywords: Histamine, Contact dermatitis,
Atopic dermatitis, Eczematous lesion, Scratching, Four histamine receptors
INTRODUCTION
Inflammatory
skin diseases, including contact dermatitis and atopic dermatitis (AD), are
often characterized by inflammation with pruritus. A major mediator of
inflammation and pruritus is histamine. Histamine is a ubiquitous chemical
messenger through four pharmacologically distinct receptors. This review
summarizes the findings regarding the roles of histamine and four histamine
receptors on the development of eczematous lesion and pruritus in allergic
dermatitis.
Eczematous Lesions Developed by Histamine in Murine
Allergic Contact Dermatitis
Mast cells and basophils mainly secret histamine in
the skin. Assessing the effect of histamine in development of eczematous
lesions, recognizing in contact dermatitis and AD, in vivo has been difficult,
as most observations involve the use of histamine receptor antagonists.
Histamine- deficient mice by disrupting the histidine decarboxylase (HDC) gene
to solve these problems were produced [1].
Plasma extravasation induced with compound 48/80,
an immediate-type response, is produced in HDC (+/+) mice but not in HDC (-/-)
mice. On the other hand, contact hypersensitivity, a delayed-type response, is
observed as a thickening of the ear skin after 2,4,6-trinitro-1- chlorobenzene
challenge and shows no difference between HDC (+/+) and HDC (-/-) mice [2].
Contact hypersensitivity is elicited by single epicutaneous applications of
contact sensitizing agent in mice previously sensitized with the same agent.
However, contact dermatitis in human usually causes by repeated epicutaneous
application of various antigens including contact sensitizing agents and
environmental allergens. Repeated epicutaneous application of contact
sensitizing agent induces epidermal hyperplasia, accumulation of large numbers of mast cells and CD4+ T cells beneath the epidermis, and
elevated serum levels of antigen-specific IgE, similar to observations of AD
[3,4]. Contact hypersensitivity response is shifted from a delayed- type
hypersensitivity to an immediate-type response by repeated application [5].
The role of histamine in the extent of chronic
eczematous lesions induced by repeated application of contact
sensitizing agent was investigated by using HDC (-/-) mice. Daily application
of diphenylcyclopropenone induces chronic allergic contact dermatitis (CACD) in
mice. Histological examination of the skin reveals that mice display
hyperplastic epidermis and mast cells and CD4+ T cells infiltration. The
magnitude of hyperplastic epidermis and inflammatory cells is more significant
in HDC (+/+) mice than HDC (-/-) ones (Figure 1) [6].
Histamine mediates chemotaxis of mast cells via the H4 receptor and is
responsible for mast cell accumulation in allergic tissues. Unique accumulation
of mast cells is presumed to be controlled by histamine through H4 receptor
binding of mast cells [7]. Infiltration of CD4+ T cells in HDC (+/+) mice is
prominent compared to infiltration of HDC (-/-) mice [6]. IL-16, the soluble
ligand for CD4+, represents a potent chemoattractant for CD4+ T cells,
eosinophils and monocytes, and is mainly derived from activated T cells [8].
IL-16 is therefore thought to be under the control
of histamine and plays an important role in the development of cell-mediated
immunity, such as delayed-type hypersensitivity reaction [9]. As lymphocytes
are stimulated to produce IL-16 by histamine via H4 receptors [10],
histamine-induced IL-16 contributes to the development of eczematous lesions in
contact dermatitis.
Levels of IL-6
and Macrophage Inflammatory Protein-2, murine homologue of human IL-8, are
increased in murine CACD [11]. Histamine enhances IL-6 and IL-8 production in
human keratinocytes in vitro [12]. IL-6 enhances B- and T-cell activation and
proliferation [13], and stimulates keratinocyte proliferation, resulting in
epidermal acanthosis [14, 15]. Keratinocytes express abundant HDC protein and
the levels increase in atopic skin [16].
Regulatory T
cells (Tregs) are a subset of T cells, which regulate effector T cells and lead
to immune tolerance to reduction of allergic reactions, and play a role in the
maintenance of immunological self-tolerance by actively suppressing
self-reactive lymphocytes [17]. Tregs suppress effector T cells and ameliorate
contact dermatitis [18]. TGF- β is one of the main regulators of Treg
recruitment in allergic lesion [19]. Since the level of TGF-β1 and the number
of Tregs in eczematous lesions is significantly higher in HDC (-/-) mice
compared to HDC (+/+) mice, histamine suppresses Tregs mediated by TGF-β1 in
the skin lesions [20]. The level of IL-10 is also suppressed by histamine in
CACD [20]. Since Th2 cell-driven allergic reactions are suppressed through
IL-10 production [21], histamine aggravates eczematous lesions by reduction of
the level of IL-10.
Th17 cells, a distinct lineage of effector CD4+ T
cells, are characterized by their production of IL-17 and IL-22 [22]. IL-17
plays an important role in activating T cells in allergen-specific
T-cell-mediated immune responses [23]. IL-17 efficiently amplifies the allergic
reaction by rendering T cells accessible to recruitment at the site of skin
inflammation in allergic contact dermatitis [24]. Th17 cells inhibit IL-4
production by Th2 cells [25]. Infiltration of IL- 17F expressing cells in CACD
is suppressed in HDC (+/+) mice compared to HDC (-/-) mice. Levels of IL-17 and
IL- 22 of skin lesions decrease in HDC (+/+) mice compared to HDC (-/-) mice
(unpublished data). These data indicate that histamine may aggravate skin
lesions of CACD by suppressing Th17 cells.
Scratching
Behavior Induced by Histamine in Murine Allergic Contact Dermatitis
Pruritus has been defined as an unpleasant
sensation that triggers a desire to scratch [26]. Contact dermatitis is known
as the common skin disease with itch sensation as the typical symptoms and is
frequently accompanied by itch-associated scratching behavior in rodents [27].
Examination of mechano-insensitive C-nociceptors has identified C- nociceptors
that respond to histamine iontophoresis in parallel with the itch rating [28].
Scratching behavior is observed in HDC (+/+) mice almost not in HDC (-/-) ones
after DCP application [29]. Scratching behavior is ameliorated in mice treated
with H1 and H4 receptor antagonist [30]. The massively increased itch in
lesional skin of patients with AD is based on sensitization for itch in the
spinal cord rather than in primary affected neuron [31]. A small number of
c-Fos (+) cells, excited sensory cells, are identified in the spinal dorsal
horn of HDC (+/+) and HDC (-/-) mice. However, remarkable increase in c-Fos (+)
cells is observed to lamina I in the dorsal horn of CACD-developed HDC (+/+)
mice, whereas it is not in CACD-developed HDC (-/-) mice. Substance P
expression in the spinal dorsal horn increases with peripheral sensory
stimulation induced from eczematous lesions [32]. Substance P expression in the
spinal dorsal horn is increased only in CACD-developed HDC (+/+) mice. Since
substance P is released from peripheral nerves, histamine is responsible for
substance P expression in the spinal dorsal horn via peripheral nerves. E-
cadherin, one of the synapse-related molecules, is expanded in the spinal
dorsal horn by peripheral sensory stimulation induced from allergic dermatitis
[32]. E-cadherin expression is increased only in the spinal dorsal horn of
CACD- developed HDC (+/+) mice. The nerve fiber proliferation and/or synapse
formation might augment itch sensation only in CACD-developed HDC (+/+) mice
[29]. Taken together, scratching behavior is mainly mediated with histamine and
the afferent pathway of sensation connects with the central nervous system
through lamina I of the spinal dorsal horn in murine CACD [29]. Pruritus is
known to be induced by a variety of mediators in addition to histamine. Primary
sensory nerves transmit the pruritic signal by protease, endothelin-1, IL-4,
IL-13, IL-31, chloroquine, and so on [33]. Mas-related G protein-couple
receptors and gastrin- releasing peptide receptor (GRPR) mediate the pruritic
sensation in primary sensory nerves and dorsal spinal cord, respectively
[34,35]. Another characteristic of pruritus in
patients with AD is its chronicity. With chronic pruritus, scratching causes
skin lesions, which in turn lead to activation of STAT3 in spinal dorsal horn
astrocytes. Induction of lipocalin 2 by astrocytes sensitizes a pruritus-
processing neuronal network involving GRPR+ spinal dorsal horn neurons, and
thereby contributes to the vicious cycle of itching and scratching and chronic
pruritus [36]. Th2 cells produce IL-31 and its receptor (IL-31 receptor A) is
expressed on primary sensory nerves [37]. Anti-IL-31 receptor A injection
inhibits pruritus in AD [38]. IL-33 signaling is functionally present in
primary sensory neurons and induces pruritus in poison ivy allergic dermatitis
[39]. Plasma levels of substance P are associated with disease activity of AD
[40]. Substance P receptor (neurokinin 1 receptor) antagonist reduces scratch
behavior in murine allergic dermatitis model [41].
Four Histamine Receptors in the Skin
A major mediator of allergic reactions and
inflammation is histamine. High amounts of histamine are released during
allergic and inflammatory disorders [42]. Histamine is a ubiquitous chemical
messenger that displays numerous functions mediated through at least four
pharmacological distinct receptors (Table 1).
H1 receptor is
expressed in keratinocytes, endothelial cells and peripheral nerves [43].
Histamine augments the production of IL-6, IL-8 and granulocyte-macrophage
colony-stimulating factor in human keratinocytes [12,44]. Histamine modulates
the differentiation from epidermal keratinocytes and impairs the skin barrier
function via H1 receptor [45]. The level of nerve growth factor is higher in AD
than in healthy controls and correlated with the severity of itch, erythema,
eosinophil count and LDH levels. The nerve growth factor level is decreased by
H1 receptor antagonist [46]. Elevated expression of periostin, which is a
matricelluar protein and contributes to tissue remodeling, is found in lesional
skin from AD patients. Histamine induces the expression of periostin and H1
receptor antagonist blocks both periostin and collagen expression
[47]. High numbers of H1 receptor expressing CD68 + macrophages are
detected in the dermis of AD skin lesions. FcɛRI stimulation promotes the
generation of H1 receptor expressing macrophage-like cells with enhanced histamine biosynthesis and H1
receptor-mediated proinflammatory properties [48]. Lack of H1 receptor
expression on dendritic cells leads to diminished IL-12, upregulated IL-23, and
IL-6 production upon allergen stimulation. H1 receptor engagement on dendritic
cells is necessary for dendritic cell activation and subsequent priming of
effector IFN-γ + CD8 + T cells [49]. The characteristic features of H1 receptor
activation in the skin are exemplified by increased vascular permeability [50]
and itching transactions [51]. H1 receptor antagonists have been successfully
used as drugs for treating allergic diseases, since these functions contribute
to allergic responses [52].
The H2 receptor
is expressed in keratinocytes, macrophages and lymphocytes [53]. Histamine
induces an increase in intracellular Ca2+ of cultured normal human
keratinocytes via H2 receptor [54]. H2 receptor stimulates the phospholipase C
signaling pathway in mouse keratinocyte [55]. Histamine-induced stimulation of
phosphodiesterase 4, which increases in blood mononuclear white cells of
patients with AD, is mediated by the H2 receptor and related to intracellular
cAMP in the human monocyte cell line [56]. H2 receptor agonist downregulates
IL-12p70 production of prestimulated human monocyte-derived dendritic cells
[57]. H2 receptor antagonist blocks histamine-induced IL-16 release from human
CD8+ T cells [10]. However, its extra function in the skin remains unclear.
The H3 receptor
is expressed in mast cells and sympathetic and parasympathetic nerves and
regulates histamine, serotonin, acetylcholine and other neurotransmitters [58].
H3 antagonist inhibits cutaneous microvascular permeability due to intradermal
injections of compound 48/80 [59]. H3 receptor antagonist increases scratching
behavior in ICR mice [60] and mast cell-deficient mice [61]. Substance P is
involved in the scratching behavior elicited by H3 receptor antagonist [62].
Histamine induces a calcium increase in the skin-specific sensory neurons via
activation of the H1 receptor and H4 receptor as well as inhibition of the H3
receptor. The decreased threshold in response to H3 receptor antagonism assumes
to activate H1 and H4 receptor on sensory neurons, which in turn results in the
excitation of histamine-sensitive afferents and therefore elicits the sensation
of itch [63]. However, the exact physiological roles of H3 receptor in the skin
remain to be explored.
H4 receptor
knockout mice show a clear amelioration of the skin lesions, with a diminished
influx of inflammatory cells and a reduced amount of IgE, a reduced number of
splenocytes and lymph node cells with a decreased number of CD4+ T cells in a
chronic model of AD [64]. The H4 receptor is upregulated during differentiation
of keratinocytes in the upper layer of epidermis versus keratinocytes in basal
layer [65]. H4 receptor is highly expressed on keratinocytes from patients with
AD and its stimulation induces keratinocyte proliferation [66]. H4 receptor is
also expressed in leukocytes and mast cells [67]. H4 receptor expression on Th2
cells is higher compared with Th1 cells and stimulation of H4 receptor results
in an induction of transcription factor AP-1 in Th2 cells, which are
dominant in allergic dermatitis [68]. H4 receptor antagonist inhibits the
production of CCL17 and CCL22, Th2 chemokine, in monocyte-derived Langerhans
cells in patients with AD [69]. Th17 cells, expressing the H4 receptor, play a
potential role in AD and the number of this cell type is associated with the
severity of AD in the acute lesions [70]. IL-17 expression is enhanced in AD
[71]. Th17 function is one of the important factors regulating allergic
diseases such as CACD and AD [72]. Natural killer cells accumulate in
eczematous lesions of AD via H4 receptor [73]. Histamine induces chemotaxis of
eosinophils through the H4 receptor [74] and rapidly induces shape changes in
eosinophils while at the same time enhancing their chemotactic response to
chemokines through the H4 receptor [74, 75]. H4 receptor also mediates histamine-induced
chemotaxis of mast cells in mouse [7, 76]. H4
receptor antagonist ameliorates CACD in HDC (+/+) mice, while H4 receptor
agonist develops CACD in HDC (-/-) ones [77]. H4 receptor is involved in
pruritic responses in mice to a greater extent than H1 receptor [78]. Taken
together, these results strongly indicate that H4 receptor antagonism is
effective for allergic dermatitis.
CONCLUSION
Histamine is related to development of eczematous lesions
and scratching behavior in murine allergic contact dermatitis. Since histamine
receptors play an important role on allergic dermatitis, anti-histamine
receptor agents are effective to treat allergic dermatitis, such as CACD and AD.
CONFLICT OF INTEREST
None declared.
1.
Ohtsu H, Tanaka S, Terui T, et al. (2001) Mice
lacking histidine decarboxylase exhibit abnormal mast cells. FEBS Lett 502: 53-56.
2.
Ohtsu H, Kuramasu A, Tanaka S, et al. (2002) Plasma
extravasation induced by dietary supplemented histamine in histamine-free mice.
Eur J Immunol 32: 1698-1708.
3.
Wang G, Savinko T, Wolff H, et al. (2007) Repeated
epicutaneous exposure to ovalbumin progressively induce atopic dermatitis-like
lesions in mice. Clin Exp Allergy 37: 151-161.
4.
Man MQ, Hatano Y, Lee SH, et al. (2008)
Characterization of a hapten-induced, murine model with multiple features of
atopic dermatitis: structural, immunologic, and biochemical changes following
single versus multiple oxazolone challenges. J Invest Dermatol 128: 79-86.
5.
Kitagaki H, Fujisawa S, Watanabe K, et al. (1995)
Immediate-type hypersensitivity response followed by a late reaction is induced
by repeated epicutaneous application of contact sensitizing agents in mice. J
Invest Dermatol 105: 749-755.
6.
Seike M, Takata T, Ikeda M, et al. (2005) Histamine
helps development of eczematous lesions in experimental contact dermatitis in
mice. Arch Dermatol Res 297: 68-74.
7.
Hofstra CL, Desai PJ, Thurmond RL, et al. (2003)
Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast
cells. J Pharmacol Exp Ther 305: 1212-1221.
8.
Kaser A, Dunzendorfer S, Offner FA, et. al. (1999) A
role for IL-16 in the cross-talk between dendritic cells and T cells. J Immunol
163: 3232-3238.
9.
Yoshimoto T, Wang CR, Yoneto T, et. al. (2000) Role
of IL-16 in delayed-type hypersensitivity reaction. Blood 95: 2869-2874.
10.
Gantner F, Sakai K, Tusche MW, et al. (2002) Histamine
h(4) and h(2) receptors control histamine- induced interleukin-16 release from
human CD8 (+) T cells. J Pharmacol Exp Ther 303: 300-307.
11.
Hamada R, Seike M, Kamijima R, et al. (2006)
Neuronal conditions of spinal cord in dermatitis are improved by olopatadine.
Eur J Pharmacol 547: 45-51.
12.
Kohda F, Koga T, Uchi H, et.al. (2002) Histamine-
induced IL-6 and IL-8 production are differently modulated by IFN-γ and IL-4 in
human keratinocytes. J Dermatol Sci 28: 34-41.
13.
Hirano T, Akira S, Taga T, et al. (1990) Biological
and clinical aspects of interleukin 6. Immunol Today 11: 443-449.
14.
Grossman RM, Krueger J, Yourish D, et al. (1989)
Interleukin 6 is expressed in high levels in psoriatic skin and stimulates
proliferation of cultured human keratinocytes. Proc Natl Acad Sci USA 86: 6367-6371.
15.
Kupper TS, Min K, Sehgal PB, et al. (1989) Production of IL-6 by keratinocytes:
implications for epidermal inflammation and immunity. Ann N Y Acad Sci 557: 454-464.
16.
Gutowska-Owsiak D, Greenwald L, Watson C, et al.
(2014) The histamine-synthesizing enzyme histindine decarboxylase is
upregulated by keratinocytes in atopic skin. Br J Dermatol 171: 771-778.
17.
Hori S, Nomura T, Sakaguchi S (2003) Control of
regulatory T cell development by the transcription factor Foxp3. Science 299:
1057-1061.
18.
Ring S, Schӓfer SC, Mahnke K, et al. (2006)
CD4+CD25+ regulatory T cells suppress contact hypersensitivity reactions by
blocking influx of effector T cells into inflamed tissue. Eur J Immunol 36:
2981-2992.
19.
Fantini MC, Becker C, Monteleone G, et al. (2004)
Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells
through Foxp3 induction and down-regulation of Smad7. J Immunol 172: 5149-5153.
20.
Tamaka K, Seike M, Hagiwara T, et al. (2015)
Histamine suppresses regulatory T cells mediated by TGF-β in murine chronic
allergic contact dermatitis. Exp Dermatol 24: 280-284.
21.
Kearley J, Barker JE, Robinson DS, et al. (2005)
Resolution of airway inflammation and hyperreactivity after in vivo transfer of
CD4+CD25+ regulatory T cells is
interleukin 10 dependent. J Exp Med 202: 1539-1547.
22.
Liang SC, Tan X, Luxenberg DP, et al. (2006)
Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively
enhance expression of antimicrobial peptides. J Exp Med 203: 2271-2279.
23.
Nakae S, Komiyama Y, Nambu A, et al. (2002)
Antigen-specific T cell sensitization is impaired in IL- 17-dificient mice,
causing suppression of allergic cellular and humoral responses. Immunity 17: 375-387.
24.
Pennino D, Eyerich K, Scarponi C, et al. (2010)
Il-17 amplifies human contact hypersensitivity by licensing hapten nonspecific
Th1 cells to kill autologous keratinocytes. J Immunol 184: 4880-4888.
25.
Yi T, Chen Y, Wang L, et al. (2009) Reciprocal
differentiation and tissue-specific pathogenesis of Th1, TH2, and Th17 cells in
graft-versus-host disease. Blood 114: 3101-3112.
26.
Ikoma A, Cevikbas F, Kempkes C, et al. (2011)
Anatomy and neurophysiology of pruritus. Semin Cutan Med Surg 30: 64-70.
27.
Nojima H, Carstens E (2003) 5-Hydroxytryptamine (5-
HT)2 receptor involvement in acute 5-HT-evoked scratching but not in
allergic pruritus induced by dinitrofluorobenzene in rats. J Pharmacol Exp
Ther, 306, 245-252.
28.
Schmelz M, Schmidt R, Bickel A, et al. (1997)
Specific C-receptors for itch in human skin. J Neurosci 17: 8003-8008.
29.
Seike M, Ikeda M, Kodama H, et al. (2005) Inhibition
of scratching behavior caused by contact dermatitis in histidine decarboxylase
gene knockout mice. Exp Dermatol 14: 169-175.
30.
Köchling H, Schaper K, Wilzopolski J, et al. (2017)
Combined treatment with H1 and H4 receptor antagonists reduces inflammation in
a mouse model of atopic dermatitis. J Dermatol Sci 87: 130-137.
31.
Ikoma A, Rukwied R, Stander S, et al. (2003) Neuronal sensitization for histamine-induced
itch in lesional skin of patients with atopic dermatitis. Arch Dermatol 139: 1455-1458.
32.
Seike M, Hamada R, Ikeda M, et al. (2005) Alteration
of sensorineural circuits in spinal cord by chronic contact dermatitis.
Somatosens Mot Res 22: 115-121.
33.
Paller AS, Kabashima K, Bieber T (2017) Therapeutic
pipeline for atopic dermatitis: End of the drought? J Allergy Clin Immunol 140: 633-643.
34.
Sun YG, Chen ZF (2007) A gastrin-releasing peptide
receptor mediates the itch sensation in the spinal cord. Nature 448: 700-703.
35.
Liu Q, Tang Z, Surdenikova L, et al. (2008) Sensory
neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced
pruritus. Cell 139: 1353-1365.
36.
Shiratori-Hayashi M, Koga K, Tozaki-Saitoh H, et al.
(2015) STAT3-dependent reactive astrogliosis in the spinal dorsal horn
underlies chronic itch. Nat Med 21: 927-931.
37.
Dillon SR, Sprecher C, Hammond A, et al. (2004)
Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in
mice. Nat Immunol 5: 752- 760.
38.
Ruzicka T, Hanifin JM, Furue M, et al. (2017) Anti-
interleukin-31 receptor a antibody for atopic
dermatitis. N Engl J Med 376: 826-835.
39.
Liu B, Tai Y, Achanta S, et al. (2016) IL-31/ST2
signaling excites sensory neurons and mediates itch response in a mouse model
of poison ivy contact allergy. Proc Natl Acad Sci U S A 113: E7572-E7579.
40.
Toyoda M, Nakamura M, Makino T, et al. (2002) Nerve
growth factor and substance P are useful plasma markers of disease activity in
atopic dermatitis. Br J Dermatol 147: 71-79.
41.
Ohmura T, Hayashi T, Satoh Y, et al. (2004)
Involvement of substance P in scratching behavior in an atopic dermatitis
model. Eur J Pharmacol 491: 191- 194.
42.
Stander S, Steinhoff M (2002) Pathophysiology of
pruritus in atopic dermatitis: an overview. Exp Dermatol 11: 12-24.
43.
Baumer W, Rossbach K (2010) Histamine as an
immunomodulator. J Dtsch Dermatol Ges 8: 495-504.
44.
Kanda N, Watanabe S (2004) Histamine enhances the
production of granulocyte-macrophage colony- stimulating factor via protein
kinase Calpha and exracellular signal-regulatyed kinase in human keratinocytes.
J Invest Dermatol 122: 863-872.
45.
Gschwandtner M, Mildner M, Mlitz V, et al. (2013)
Histamine suppresses epidermal keratinocyte differentiation and impairs skin
barrier function in a human skin model. Allergy 68: 37-47.
46.
Yamaguchi J, Aihara M, Kobayashi Y, et al. (2009)
Quantitative analysis of nerve growth factor (NGF) in the atopic dermatitis and
psoriasis horny layer and effect of treatment on NGF in atopic dermatitis. J
Dermatol Sci 53: 48-54.
47.
Yang L, Murota H, Serada S, et al. (2014) Histamine
contributes to tissue remodeling via periostin expression. J Invest Dermatol
134: 2105-2113.
48.
Novak N, Peng WM, Bieber T, et al. (2013) FcɛRI
stimulation promotes the differentiation of histamine receptor 1-expressing
inflammatory macrophages. Allergy 68: 454-461.
49.
Vanbervliet B, Akdis M, Vocanson M, et al. (2011)
Histamine receptor H1 signaling on dendritic cells plays a key role in the
IFN-γ/IL-17 balance in T cell- mediated skin inflammation. J Allergy Clin
Immunol 127: 943-953.
50.
Sercombe R, Verrecchia C, Philipson V, et al. (1986)
Histmaine-induced constriction and dilatation of rabbit middle cerebral
arteries in vitro: role of the endothelium. Blood Vessels 23: 137-153.
51.
Hagermark O, Strandberg K, Gronneberg R (1979)
Effects of histamine receptor antagonists on histamine- induced responses in
human skin. Acta dermato- venereologica 59:
297-300.
52.
Simons FE, Simons KJ (2011) Histamine and H1-
antihistamines: celebrating a century of progress. J Allergy Clin Immunol 128: 1139-1150.
53.
Akdis CA, Simons FE (2006) Histamine receptor are
hot in immunopharmacology. Eur J Pharmacol 533: 69-76.
54.
Koizumi H, Ohkawara A (1999) H2 histamine
receptor-mediated increase in intracellular Ca2+ in cultured human
keratinocytes. J Dermatol Sci 21: 127- 132.
55.
Fitzsimons C, Durăn H, Engel N, et al. (1999)
Changes in H2 receptor expression and coupling during Ca2+- induced
differentiation in mouse epidermal keratinocytes. Inflamm Res 48: Suppl 1 S73-74.
56.
Delgado M, Fuentes JA, Fernandez-Alfonso MS (2003)
Histamine up-regulates phosphodiesterase IV activity in U-937 cells through H2
receptor stimulation and cAMP increase. Med Sci Monit 9: BR212-219.
57.
Gutzmer R, Langer K, Lisewski M, et al. (2002)
Expression and function of histamine receptors 1 and 2 on human monocyte-derived
dendritic cells. J Allergy Clin Immunol 109:
524-531.
58.
Sander K, Kottke T, Stark H (2008) Histamine H3
receptor antagonists go to clinics. Biol Pharm Bull 31: 2163-2181.
59.
McLeod RL, Mingo GG, Kreutner W, et al. (2005)
Effect of combined histamine H1 and H3 receptor blockade on cutaneous
microvascular permeability elicited by compound 48/80. Life Sci 76: 1787-1794.
60.
Sugimoto Y, Iba Y, Nakamura Y, et al. (2004)
Pruritus-associated response mediated by cutaneous histamine H3 receptors. Clin
Exp Allergy 34: 456-459.
61.
Hossen MA, Sugimoto Y, Kayasuga R, et al. (2003)
Involvement of histamine H3 receptors in scratching behaviour in mast
cell-deficient mice. Br J Dermatol 149: 17-22.
62.
Hossen MA, Inoue T, Shinmei Y, et al. (2006) Role of
substance P on histamine H(3) antagonist-induced scratching behavior in mice. J
Pharmacol Sci 100: 297- 302.
63.
Rossbach K, Nassenstein C, Gschwandtner M, et al.
(2011) Histamine H1, H3 and H4 receptors are involved in pruritus. Neuroscience
190: 89-102.
64.
Rossbach K, Schaper K, Kloth Ch, et al. (2016)
Histamine H4 receptor knockout mice display reduced inflammation in a chronic
model of atopic dermatitis. Allergy 71: 189-197.
65.
Yamaura K, Oda M, Suwa E, et al. (2009) Expression
of histamine H4 receptor in human epidermal tissues and attenuation of
experimental pruritus using H4 receptor antagonist. J Toxico Sci 34: 427-431.
66.
Glatzer F, Gschwandtner M, Ehling S, et al. (2013)
Histamine induces proliferation in keratinocytes from patients with atopic
dermatitis through the histamine 4 receptor. J Allergy Clin Immunol 132: 1358-1367.
67.
Oda T, Morikawa N, Saito Y, et al. (2000) Molecular
cloning and characterization of a novel type of histamine receptor
preferentially expressed in leukocytes. J Biol Chem 275: 36781-36786.
68.
Gutzmer R, Mommert S, Gschwandtner M, et al. (2009)
The histamine H4 receptor is functionally expressed on T(H)2 cells. J Allergy
Clin Immunol 123: 619-625.
69.
Miyano K, Matsushita S, Tsuchida T, et al. (2016)
Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22
production by monocyte- derived Langerhans cells in patients with atopic
dermatitis. J Dermatol 43: 1024-1029.
70.
Koga C, Kabashima K, Shiraishi N, et al. (2008)
Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Drematol
128: 2625-2630.
71.
Batista DI, Perez L, Orfail RL, et al. (2015)
Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17
cytokines in adults with atopic dermatitis. J Eur Acad Dermatol Venereol 29:
1091- 1095.
72.
Matsushita A, Seike M, Hagiwara T, et al. (2014)
Close relationship between T helper (Th) 17 and Th2 response in murine ACD.
Clin Exp Dermatol 39: 924- 931.
73.
Ehling S, Rossbach K, Dunston SM, et al. (2016)
Allergic inflammation is augmented via histamine H4 receptor activation: The
role of natural killer cells in vitro and in vivo. J Dermatol Sci 83: 106-115.
74.
Ling P, Ngo K, Nguyen S, et al. (2004) Histamine H4
receptor mediates eosinophil chemotaxis with cell shape and adhesion molecule
upregulation. Br J Pharmacol 142: 161-171.
75.
Buckland KF, Williams TJ, Conroy DM (2003) Histamine
induces cytoskeletal changes in human eosinophils via the H(4) receptor. Br J
Pharmacol 140: 1117-1127.
76.
Thurmond RL, Desai PJ, Dunford PJ, et al. (2004) A
potent and selective histamine H4 receptor antagonist with anti-inflammatory
properties. J Pharmacol Exp Ther 309: 404-413.
77.
Seike M, Furuya K, Omura M, et al. (2010) Histamine
H4 receptor antagonist ameliorates chronic allergic contact dermatitis induced
by repeated challenge. Allergy 65: 319-326.
78.
Dunford PJ, Williams KN, Desai PJ, et al. (2007)
Histamine H4 receptor antagonists are superior to traditional antihistamines in
the attenuation of experimental pruritus. J Allergy Clin Immunol 119: 176-183.
QUICK LINKS
- SUBMIT MANUSCRIPT
- RECOMMEND THE JOURNAL
-
SUBSCRIBE FOR ALERTS
RELATED JOURNALS
- International Journal of Surgery and Invasive Procedures (ISSN:2640-0820)
- Oncology Clinics and Research (ISSN: 2643-055X)
- Journal of Clinical Trials and Research (ISSN:2637-7373)
- Journal of Renal Transplantation Science (ISSN:2640-0847)
- International Journal of AIDS (ISSN: 2644-3023)
- Journal of Spine Diseases
- Journal of Cell Signaling & Damage-Associated Molecular Patterns