Histamine receptor H4R-selective ligands influence the STAT6 Transcription Activation Domain (TAD) and the DNA-binding

Michel, I.; Borck, H.; McElligott, Sandra; Krieg, Carsten; Diel, F.

doi:10.1007/s00011-007-0623-1

Cited by 12 publications

(11 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A hallmark of the H2R signaling pathway is the formation of cAMP [55], while H4R signals through G i/o receptors, resulting in inhibition of forskolin-induced cAMP production, intracellular calcium mobilization, and actin polymerization [40,55,56]. In addition, H4R has been reported to activate mitogen-activated protein kinases [57] and the JAK/STAT signaling pathway [58,59]. Importantly, histamine receptors can form dimers and oligomers, which allow interaction among histamine receptors as well as other G protein-coupled receptors, and this further increases the complexities of downstream signaling events in response to histamine stimulation.…”

Section: Histamine Overviewmentioning

confidence: 99%

Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

Benedetto

Yoshida

Fridy

et al. 2015

JCM

View full text Add to dashboard Cite

Atopic Dermatitis (AD), the most common chronic inflammatory skin disease, is characterized by an overactive immune response to a host of environmental allergens and dry, itchy skin. Over the past decade important discoveries have demonstrated that AD develops in part from genetic and/or acquired defects in the skin barrier. Histamine is an aminergic neurotransmitter involved in physiologic and pathologic processes such as pruritus, inflammation, and vascular leak. Enhanced histamine release has been observed in the skin of patients with AD and antihistamines are often prescribed for their sedating and anti-itch properties. Recent evidence suggests that histamine also inhibits the terminal differentiation of keratinocytes and impairs the skin barrier, raising the question whether histamine might play a role in AD barrier impairment. This, coupled with the notion that histamine’s effects mediated through the recently identified histamine receptor H4R, may be important in allergic inflammation, has renewed interest in this mediator in allergic diseases. In this paper we summarize the current knowledge on histamine and histamine receptor antagonists in AD and skin barrier function.

show abstract

Section: Histamine Overviewmentioning

confidence: 99%

Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

Benedetto

Yoshida

Fridy

et al. 2015

JCM

View full text Add to dashboard Cite

show abstract

“…The participation of the H 4 receptor in different aspects of inflammation, such as chemotaxis, upregulation of adhesion molecules and modulation of cytokine secretion, is suggested based on a variety of in vitro studies using inflammatory cells from different mammalian species. 4,[12][13][14][15][16][17][18][19][20][21][22][23] Recently, the role of the H 4 receptor in Figure 2. Tissue distribution of canine H 4 receptor mRNA determined by RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

“…Various in vitro and in vivo studies have shown the participation of this receptor in inflammatory and immune responses, including eosinophil, mast cell, T‐cell and dendritic cellchemotaxis, in addition to inhibition of interleukin‐12 secretion by dendritic cells and increase of interleukin‐16 release by T cells 12–18 . However, the data on cytokine and chemokine immune response modulation by histamine and its receptors is rather controversial, particularly in regards to T‐helper 1 (Th1) and T‐helper 2 (Th2) polarization 19–23 . Interesting, Dijkstra et al.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14][15][16][17][18] However, the data on cytokine and chemokine immune response modulation by histamine and its receptors is rather controversial, particularly in regards to T-helper 1 (Th1) and T-helper 2 (Th2) polarization. [19][20][21][22][23] Interesting, Dijkstra et al suggested that H 4 agonists, not antagonists, should be considered as anti-inflammatory thera-pies after showing that this receptor, expressed on human inflammatory dendritic epidermal cells, downregulates Th1-and Th2-related cytokines and chemotatic activity. 23 Recently, the expression of H 4 receptor was also demonstrated in human dermal fibroblasts, mast cells and keratinocytes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The expression of histamine H₄ receptor mRNA in the skin and other tissues of normal dogs

Eisenschenk¹,

Torres²,

Oliveira³

et al. 2011

Veterinary Dermatology

View full text Add to dashboard Cite

The histamine 4 (H(4)) receptor was first cloned and characterized in 2000 using the human H(3) receptor DNA sequence. The H(4) receptor has been shown to participate in various aspects of inflammation, such as chemotaxis, upregulation of adhesion molecule expression and modulation of cytokine secretion. The primary goal of this study was to determine whether H(4) receptor mRNA is expressed in normal canine skin by performing an RT-PCR. An additional goal was to determine the expression of this receptor in the colon, liver, spleen and kidney. Tissues were collected from five healthy, young-adult pit bull dogs. Samples were immediately placed in RNAlater(®) solution and stored at -20°C until processed. The amplified products in all skin samples in addition to the colon, liver, spleen and kidney (variable expression) had the expected size of 400-500 bp. The sequenced amplicons matched the National Center for Biotechnology Information published sequence for the canine H(4) receptor. The study results showed that canine normal skin expresses the H(4) receptor mRNA. Further studies using immunohistochemistry should be conducted to demonstrate the expression of the H(4) receptor at the protein level and to localize the expression of this receptor in the skin.

show abstract

“…

Material and methods

Human PBMC from 5 atopic/non-atopic volunteers (IgE > 500 IU/ml, normal age matched controls: < 50 IU/ml) were stimulated by PHA and anti-CD3/IL-2 (1 ng/ml) in 3-day cultures.

…”

mentioning

confidence: 99%

Th17 in sensitized human lymphocytes ex vivo ?

Haefner

Krieg²,

Michel³

et al. 2009

Inflamm. Res.

Self Cite

View full text Add to dashboard Cite

IntroductionIn recent work we could show that sensitized human T lymphocytes reveal altered STAT6/STAT1 in terms of DNA binding balance compared to normal controls [1,2]. As STAT3 is specific for Th17 signal transduction, and this cell type can play a dominant role in B cell regulation and induction of allergic, inflammatory and autoimmune disorders [3, for review 4], the aim of this paper was to investigate STAT3 activation in the down stream regulation of circulating human lymphocytes ex vivo. Material and methodsHuman PBMC from 5 atopic/non-atopic volunteers (IgE > 500 IU/ml, normal age matched controls: < 50 IU/ml) were stimulated by PHA and anti-CD3/IL-2 (1 ng/ml) in 3-day cultures. Allergic patients were suffering from seasonal hay fever and chronic atopic eczema. IL-23 (10 ng/ml) and histamine (2.5 mM) were added 4 hours post-plated. Cytokines were measured by enzyme linked immune sorbent assay (ELISA) and STAT-DNA interaction by electrophoretic mobility shift assay (EMSA), respectively. For EMSA, the infrared dye labelled double stranded DNA oligonucleotide STAT3 5'GAT CCT TCT GGG AAT TCC TAG ATC 3' (LI-COR Nebraska USA) was applied. PBMC differentiation was identified using cytoflow/FACS analyses. EMSA results were processed using the Gelscan V 5.1 software: P < 0.05 was considered statistically significant. Results and discussionIt could be shown that IL-17E as well as IL-4 was constitutively increased in the atopic samples and that anti-CD3 was a more effective stimulator than PHA compared to the non-atopic matched controls (Tab. 1). For IL-4, PHA was more effective than both anti-CD3 and IFN-g in the non-atopic group (p < 0.05, n = 5, Student t). The most augmented IL-17E-responses could be demonstrated in non-atopics using IL-23 as a stimulator (Tab. 1). The contrary effect was observed in the atopic group, where the initially high levels of IL-17E were down-regulated corresponding to the increase of Th1 (IFN-g) polarization. This is in a good accordance to recent work, where the IL-23/Th17-axis was shown to be the predominant regulator of inflammatory and allergic disorders [5]. In terms of a potential negative feedback of histamine it could be demonstrated that the lymphocyte proliferation and Th1 activity (IFN-g) was increased, thereby inducing down-regulation of the Th2/Th17-IL-17E activity (data not shown). This is in a good agreement to the recent observation indicating that histamine feedback responses were strongly concentration-dependent in human lymphocytes ex vivo [6]. Surprisingly, anti-CD3-stimulated DNA binding of STAT3 was suppressed after Th17-stimulatory IL-23 activation in the presence of IL-1ß with an inverse effect in the atopic group (Fig. 1). After addition of histamine (2.5 mM) the responses turned into the contrary. There was an increase in the atopic group but inhibition in the non-atopic group as it was demonstrated also for STAT1 in recent work [6].From these results it could be concluded that Th17 showed downstream regulatory potency with specific differences in atopic pat...

show abstract

Histamine receptor H4R-selective ligands influence the STAT6 Transcription Activation Domain (TAD) and the DNA-binding

Cited by 12 publications

References 5 publications

Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

The expression of histamine H₄ receptor mRNA in the skin and other tissues of normal dogs

Th17 in sensitized human lymphocytes ex vivo ?

Contact Info

Product

Resources

About

Histamine receptor H4R-selective ligands influence the STAT6 Transcription Activation Domain (TAD) and the DNA-binding

Cited by 12 publications

References 5 publications

Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

The expression of histamine H4 receptor mRNA in the skin and other tissues of normal dogs

Th17 in sensitized human lymphocytes ex vivo ?

Contact Info

Product

Resources

About

The expression of histamine H₄ receptor mRNA in the skin and other tissues of normal dogs