Histamine inhibits the production of interleukin-12 through interaction with H2 receptors.

Kraan, Tineke C. T. M. van der Pouw; Snijders, A.; Boeije, L. C. M.; Groot, Els R. de; Alewijnse, Astrid E.; Leurs, Rob; Aarden, Lucien A.

doi:10.1172/jci3692

Cited by 189 publications

(122 citation statements)

References 69 publications

(45 reference statements)

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“…Histamine has been shown to decrease the production of IL12p70 of monocytes (35,36) and MoDC (10 -13) via the H2R. We show here that histamine also blocked IL-12p70 production of polyIC stimulated MoDC via the H4R as shown directly by the H4R agonist clobenpropit and indirectly by the H3R/H4R antagonist thioperamide (Fig.…”

Section: Effects On Il-12p70 and Il-10 Productionsupporting

confidence: 65%

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Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Gutzmer

Diestel

Mommert

et al. 2005

The Journal of Immunology

220

249

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There is increasing evidence that histamine as an important mediator of immediate type allergic reactions also effects professional APCs. Recent reports showed effects of histamine on human monocyte-derived dendritic cells (MoDC) mediated primarily via histamine H1 receptors (H1R) and H2R. We show here that MoDC also express H3R and H4R at the mRNA and protein level. mRNA of the H3R is down-regulated and mRNA of the H4R is up-regulated during the differentiation from monocytes to MoDC. H4R or H2R stimulation suppressed IL-12p70 production in MoDC. Induction of cAMP was necessary for IL-12p70 inhibition mediated via the H2R. In contrast, H4R stimulation did not affect cAMP production but induced the transcription factor AP-1, and U0126, an inhibitor of AP-1 transactivation and MEK, rescued H4R mediated IL-12p70 suppression. Moreover, MoDC responded to a H4R agonist (and also to a H2R agonist) with increased F-actin polymerization and migration in modified Boyden chamber assays, suggesting a chemotactic effect of histamine via the H2R and the H4R. Thus, H4R stimulation on MoDC results in immunomodulatory and chemotactic effects. Histamine induces chemotaxis and IL-12p70 suppression via different receptors using different signaling pathways, which might be important for the pathogenesis of and therapeutic interventions in allergic diseases.

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Section: Effects On Il-12p70 and Il-10 Productionsupporting

confidence: 65%

“…The ability of the G␣ s -coupled H2R to induce cAMP in monocytes and MoDC has been described previously (11,12,35,36). Many of such G␣ scoupled, cAMP-inducing receptors have been reported to block IL-12p70 (reviewed in Ref.…”

Section: Discussionmentioning

confidence: 93%

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Gutzmer

Diestel

Mommert

et al. 2005

The Journal of Immunology

220

249

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“…Several studies have started to highlight the complexity of histamine's effects on cytokine network in human cells depending on the type of receptor activated. For example, activation of IL-6 production generally occurs via H 1 receptors (54 -56), whereas inhibition of IL-1, TNF-␣, and IL-12 production by LPS-stimulated human monocytes is mediated by H 2 receptors (35,36,57). Furthermore, activation of H 2 and H 3 receptors stimulates IL-10 release from human monocytes and macrophages (11,25).…”

Section: Discussionmentioning

confidence: 99%

“…Although histamine has been reported either to induce (25,34) or inhibit (35,36) cytokine synthesis in human monocytes and macrophages, there are no data on the effect of this mediator on IL-6, a major cytokine produced by human macrophages (37). In these experiments, macrophages were incubated with increasing concentrations of histamine ranging from 10 Ϫ9 to 10 Ϫ6 M for 6 h at 37°C.…”

Section: Effect Of Histamine On Il-6 Production From Human Lung Macromentioning

confidence: 99%

Histamine Induces Exocytosis and IL-6 Production from Human Lung Macrophages Through Interaction with H1 Receptors

Triggiani

Gentile

Secondo

et al. 2001

The Journal of Immunology

133

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Increasing evidence suggests that a continuous release of histamine from mast cells occurs in the airways of asthmatic patients and that histamine may modulate functions of other inflammatory cells such as macrophages. In the present study histamine (10−9–10−6 M) increased in a concentration-dependent fashion the basal release of β-glucuronidase (EC50 = 8.2 ± 3.5 × 10−9 M) and IL-6 (EC50 = 9.3 ± 2.9 × 10−8 M) from human lung macrophages. Enhancement of β-glucuronidase release induced by histamine was evident after 30 min and peaked at 90 min, whereas that of IL-6 required 2–6 h of incubation. These effects were reproduced by the H1 agonist (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)heptane carboxamide but not by the H2 agonist dimaprit. Furthermore, histamine induced a concentration-dependent increase of intracellular Ca2+ concentrations ([Ca2+]i) that followed three types of response, one characterized by a rapid increase, a second in which [Ca2+]i displays a slow but progressive increase, and a third characterized by an oscillatory pattern. Histamine-induced β-glucuronidase and IL-6 release and [Ca2+]i elevation were inhibited by the selective H1 antagonist fexofenadine (10−7–10−4 M), but not by the H2 antagonist ranitidine. Inhibition of histamine-induced β-glucuronidase and IL-6 release by fexofenadine was concentration dependent and displayed the characteristics of a competitive antagonism (Kd = 89 nM). These data demonstrate that histamine induces exocytosis and IL-6 production from human macrophages by activating H1 receptor and by increasing [Ca2+]i and they suggest that histamine may play a relevant role in the long-term sustainment of allergic inflammation in the airways.

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“…There were also some modulated genes with important anti-inflammatory properties in 6-dpf fish: the histamine receptor H2 (HRH2), that acts as a suppressor of antigen presentation capacity and enhances IL10 production [58][59][60][61][62][63] and the toll IL1 receptor domain-containing adaptor (SARM1) that down-modulates NFKB and IRF3-mediated TLR3 and TLR4 signaling. 64 Similar to the LD treatment, some proteins related to tissue damage and apoptosis were also modulated in zebrafish in response to the SLD treatment, but the inflammatory effects did not seem to be as apparent as for the lethal treatment.…”

Section: Dios Et Almentioning

confidence: 99%

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

Dios

Balseiro²,

Costa³

et al. 2014

Zebrafish

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Septic shock is the most common cause of death in intensive care units due to an aggressive inflammatory response that leads to multiple organ failure. However, a lipopolysaccharide (LPS) tolerance phenomenon (a nonreaction to LPS), is also often described. Neither the inflammatory response nor the tolerance is completely understood. In this work, both of these responses were analyzed using microarrays in zebrafish. Fish that were 4 or 6 days postfertilization (dpf) and received a lethal dose (LD) of LPS exhibited 100% mortality in a few days. Their transcriptome profile, even at 4 dpf, resembled the profile in humans with severe sepsis. Moreover, we selected 4-dpf fish to set up a tolerance protocol: fish treated with a nonlethal concentration of Escherichia coli LPS exhibited complete protection against the LD of LPS. Most of the main inflammatory molecules described in mammals were represented in the zebrafish microarray experiments. Additionally and focusing on this tolerance response, the use of cyclodextrins may mobilize cholesterol reservoirs to decrease mortality after a LD dose of LPS. Therefore, it is possible that the use of the whole animal could provide some clues to enhance the understanding of the inflammatory/tolerance response and to guide drug discovery.

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Histamine inhibits the production of interleukin-12 through interaction with H2 receptors.

Cited by 189 publications

References 69 publications

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Histamine Induces Exocytosis and IL-6 Production from Human Lung Macrophages Through Interaction with H1 Receptors

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

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