Regulation of the immune response and inflammation by histamine and histamine receptors

O’Mahony, Liam; Akdiş, Mübeccel; Akdiş, Cezmi A.

doi:10.1016/j.jaci.2011.06.051

Cited by 260 publications

(227 citation statements)

References 134 publications

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“…When we looked at functional effects of histamine on mDCs we observed that mDCs stimulated with TLR4 and TLR2 agonists changed their cytokines profile in the following way: Th1 polarizing cytokine IL12p70 and TNF␣ were equally produced by LPS and Pam3Cys, whereas IL10, an anti-inflammatory cytokine, IL6 and the Th1 chemoattracting CXCL10 were produced at a significantly higher level by LPS compared with Pam3Cys-stimulated cells. In agreement with other authors' results, histamine modulates this profile and reduces both TLRs induced IL12p70 and CXCL10 production (15,29,30). On the other hand, we did not confirm previous data showing that histamine determines TNF␣ reduction in TLR2-activated cells, nor that histamine increases IL10 by TLR4-and TLR2-stimulated mDCs (11,13,15,29).…”

Section: Discussionsupporting

confidence: 67%

Histamine Regulates Actin Cytoskeleton in Human Toll-like Receptor 4-activated Monocyte-derived Dendritic Cells Tuning CD4+ T Lymphocyte Response

Aldinucci¹,

Bonechi²,

Manuelli³

et al. 2016

Journal of Biological Chemistry

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Histamine, a major mediator in allergic diseases, differentially regulates the polarizing ability of dendritic cells after Tolllike receptor (TLR) stimulation, by not completely explained mechanisms. In this study we investigated the effects of histamine on innate immune reaction during the response of human monocyte-derived DCs (mDCs) to different TLR stimuli: LPS, specific for TLR4, and Pam3Cys, specific for heterodimer molecule TLR1/TLR2. We investigated actin remodeling induced by histamine together with mDCs phenotype, cytokine production, and the stimulatory and polarizing ability of Th0. By confocal microscopy and RT-PCR expression of Rac1/CdC42 Rho GTPases, responsible for actin remodeling, we show that histamine selectively modifies actin cytoskeleton organization induced by TLR4, but not TLR2 and this correlates with increased IL4 production and decreased IFN␥ by primed T cells. We also demonstrate that histamine-induced cytoskeleton organization is at least in part mediated by down-regulation of small Rho GTPase CdC42 and the protein target PAK1, but not by down-regulation of Rac1. The presence and relative expression of histamine receptors HR1-4 and TLRs were determined as well. Independently of actin remodeling, histamine downregulates IL12p70 and CXCL10 production in mDCs after TLR2 and TLR4 stimulation. We also observed a trend of IL10 up-regulation that, despite previous reports, did not reach statistical significance.

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Section: Discussionsupporting

confidence: 67%

Histamine Regulates Actin Cytoskeleton in Human Toll-like Receptor 4-activated Monocyte-derived Dendritic Cells Tuning CD4+ T Lymphocyte Response

Aldinucci¹,

Bonechi²,

Manuelli³

et al. 2016

Journal of Biological Chemistry

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“…Meanwhile, recent antihistamine research has focused on H 4 -antagonists; the H 4 -receptor seems important for the chemoattraction of immunologically relevant cells (eosinophils, mast cells, neutrophils, T-cells, dendritic cells) [51], making H 4 -antihistamines promising in potentially modulating the pro-allergic function of these cells [52,53].…”

Section: Pharmacotherapymentioning

confidence: 99%

Pediatric Allergic Rhinitis and Asthma: Can the March be Halted?

et al. 2013

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The strong epidemiologic and pathophysiologic link between allergic rhinitis (AR) and asthma has led to the concept of 'united airways disease' or 'respiratory allergy', implying that allergy, in its widest sense, underlies this clinical syndrome. Progression from AR to asthma is frequent and part of the 'atopic march'. Since pediatric immune responses are more adaptable and therefore may be more amenable to treatment, interventions at early childhood are characterized by a higher chance to affect the natural history of respiratory allergy. Although current treatments are quite effective in alleviating respiratory allergy symptoms, it has proven much more difficult to confirm any influence on the progression of the disease. Much more promising is the field of specific allergen immunotherapy, where current evidence, although not yet of ideal robustness, points towards a disease-modifying effect. In addition, newer or emerging, possibly more effective or more targeted interventions are promising in the preventive sense.

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“…Histamine is generated by several cells during the immune response not only through the release of intracellular stores in mast cells or basophils in response to IgE-dependent or -independent stimuli, but also through de novo synthesis, catalysed by histidine decarboxylase, in a number of haemapoietic cells that secrete the amine immediately without prior storage. These features enable histamine to finely tune the delicate balance between immunity and tolerance by affecting the polarization and cytokine production of dendritic cells, immunoregulatory cells, natural killer cells, epithelial cells, B-lymphocytes and T-lymphocytes, so providing new pharmacological strategies to control immune reactivity during immune disorders, such as autoimmunity (O'Mahony et al, 2011). Histamine and its four receptors represent a complex system of immunoregulation with distinct effects dependent on receptor subtype and their differential expression.…”

Section: Effects Of Histamine On the Immune Systemmentioning

confidence: 99%

“…These are influenced by the stage of cell differentiation, as well as the microenvironment, leading to the selective recruitment of effector cells into tissue sites accompanied by effects on cellular maturation, activation, polarization and effector functions, which can lead to tolerogenic or pro-inflammatory responses. It is clear that the effects of histamine on the homeostasis of the immune system are dependent on the expression and activity of the four currently known histamine receptors (O'Mahony et al, 2011;Ferstl et al, 2012). However, 100 years after the original identification of histamine, the complex regulatory interactions between histamine and the host immune response to everyday microbial and environmental challenges are still not fully understood.…”

mentioning

confidence: 99%

Modulation of neutrophil oxidative burst via histamine receptors

Čı́ž

Lojek

2013

British J Pharmacology

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Histamine has the ability to influence the activity of immune cells including neutrophils and plays a pivotal role in inflammatory processes, which are a complex network of cellular and humoral events. One of the main functions manifested by activated neutrophils is oxidative burst, which is linked to the production of reactive oxygen species; therefore, the effects of histamine receptor agonists and antagonists on the oxidative burst of neutrophils is reviewed. A role for the well-characterized histamine H1 and H2 receptors in this process is discussed and compared to that of the recently discovered H4 receptor. LINKED ARTICLESThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 AbbreviationsCaI, calcium ionophore A23187; N-fMLP, N-formyl-methionyl-leucyl-phenylalanine; OZP, opsonized zymosan particle; PMA, phorbol myristate acetate; ROS, reactive oxygen species; TLR, toll-like receptor Oxidative burst of neutrophilsNeutrophils are the most abundant type of white blood cells, comprising about 50-70% of all leukocytes. One of the most important defence mechanisms of neutrophils is associated with their ability to mediate a strong oxidative burst through the formation of reactive oxygen species (ROS). While oxidative burst is important for the elimination of invading microorganisms, the overproduction of ROS or the impairment of endogenous antioxidant defences may result in detrimental effects on the host's own cells and tissues (Freitas et al., 2009). Neutrophil oxidative burst is accompanied by the production of NADPH oxidase, which reduces oxygen to a superoxide anion radical. It is generally assumed that the NADPH oxidase is activated exclusively in the plasma membrane. However, in neutrophils, this assumption does not fit with the subcellular localization of the membrane components of the NADPH oxidase, which are stored in the granular compartments, and it has become increasingly evident that oxidants are also produced in an intracellular compartment, identified as specific granules. Myeloperoxidase is stored in another subset of granules, the azurophil granules, and participates in the processing of the ROS. In fact, it has been suggested that neutrophil activation is accompanied by the fusion of azurophil with specific granules, allowing these peroxidase-dependent reactions to take place (Karlsson and Dahlgren, 2002). PKC-d is required for full production of NADPH oxidase and activation of the respiratory burst. Neutrophils also express PKC-a and b, which may be involved in adhesion, degranulation and phagocytosis, but the evidence for this is not yet conclusive (Bertram and Ley, 2011). Although the complex mechanisms that coordinate the membrane traffic, oxidative burst and release of granule contents required for the microbicidal activities of neutrophils are not completely understood, it is evident that they are unique and differ from those in macrophages (Nordenfelt and Tapper, 2011). Neutr...

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Regulation of the immune response and inflammation by histamine and histamine receptors

Cited by 260 publications

References 134 publications

Histamine Regulates Actin Cytoskeleton in Human Toll-like Receptor 4-activated Monocyte-derived Dendritic Cells Tuning CD4+ T Lymphocyte Response

Histamine Regulates Actin Cytoskeleton in Human Toll-like Receptor 4-activated Monocyte-derived Dendritic Cells Tuning CD4+ T Lymphocyte Response

Pediatric Allergic Rhinitis and Asthma: Can the March be Halted?

Modulation of neutrophil oxidative burst via histamine receptors

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