Interference of methysergide, a specific 5‐hydroxytryptamine receptor antagonist, with airway chronic allergic inflammation and remodelling in a murine model of asthma

Lima, Carla; Souza, Valdênia Maria Oliveira de; Soares, Alexandre Learth; Macedo, Mahasti Sahihi de; Tavares-de-Lima, Wothan; Vargäftig, B. Boris

doi:10.1111/j.1365-2222.2007.02700.x

Cited by 31 publications

(22 citation statements)

References 68 publications

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“…We have previously shown that Aspergillus fumigates –induced increases of IgE in airways are associated with eosinophil-dependent AHR24; others have reported an attenuation of allergen-induced increases in IgE by histamine and serotonin antagonists 25,26. Using an IgE passive sensitization model in human small airways to replicate atopic conditions,22,23 the effects of C-027 on IgE passively sensitized induced bronchoconstriction were examined.…”

Section: Discussionmentioning

confidence: 99%

C-027 Inhibits IgE-mediated passive sensitization bronchoconstriction and acts as a histamine and serotonin antagonist in human airways

Cooper

Zhang²,

Damera³

et al. 2011

allergy asthma proc

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Atopic asthma is poorly controlled by current therapies. Newer therapies and novel antihistamines are, therefore, required to treat patients whose atopic asthma is not controlled. For the first time, C-027 is shown to antagonize histamine, IgE-mediated and serotonin-induced contraction in human airways and vessels. Human precision-cut lung slices (PCLS, 250 µm thick), containing an airway or blood vessel, were pretreated with either C-027 (2 hours) or with vehicle alone and were contracted with histamine or serotonin. Known antihistamine was used as a comparator in antihistamine studies. Also, human airways were contracted via IgE passive sensitization in the presence or absence of C-027 or fexofenadine. Affinity of C-027 toward human G-protein coupled receptors was also determined, as well as the drug's biodistribution in murine model. C-027 was shown to have the highest affinity toward human histamine and serotonin receptors. Subsequently, C-027 was shown to antagonize histamine- and serotonin-induced airway and vascular smooth muscle contraction, respectively, and histamine-released bronchocontraction mediated by IgE passive sensitization in human small airways. C-027 also inhibited histamine-mediated single-cell calcium ion release. Low levels of C-027 were found in murine brain tissue. Collectively, these data suggest that C-027 markedly inhibits IgE-induced bronchoconstriction and antagonizes histamine and serotonin-contraction with little biodistribution in the brain. The compound may offer a future therapy for allergen-induced airway hyperresponsiveness in patients with asthma.

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Section: Discussionmentioning

confidence: 99%

C-027 Inhibits IgE-mediated passive sensitization bronchoconstriction and acts as a histamine and serotonin antagonist in human airways

Cooper

Zhang²,

Damera³

et al. 2011

allergy asthma proc

View full text Add to dashboard Cite

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“…Some studies report that serotonin is closely linked to inflammatory responses, including the induction of mast cell adhesion and migration, activation of alveolar macrophages, and development and maintenance of arterial remodeling through the release of cytokines [33][34][35] . It is found that fluoxetine has anti-inflammatory properties and that there is a positive correlation between SERT and cytokine mRNA expression in patients with depression, who are affected by chronic treatment with fluoxetine [22] .…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine inhibited extracellular matrix of pulmonary artery and inflammation of lungs in monocrotaline-treated rats

Wang

Yang

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine on extracellular matrix (ECM) remodeling of the pulmonary artery and inflammation of the lungs in pulmonary arterial hypertension (PAH) induced by monocrotaline in rats. Methods: MCT-induced chronic PAH was established in Wistar rats. After treatment with fluoxetine for 3 weeks, pulmonary hemodynamic measurement and morphological investigation of lung tissues were undertaken. The main components of the ECM, elastin and collagen, were detected using Van Gieson stain and Orcein stain, respectively, or using Victoria-ponceau's double stain. The ECM proteolytic enzymes matrix metalloproteinase (MMP)-2 and MMP-9, and the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, were detected by Western blot. Inflammation of lung tissue was assayed using lung morphology and inflammatory cytokine expression. Results: Fluoxetine (2 and 10 mg/kg) significantly inhibited MCT-induced PAH, attenuated pulmonary arterial muscularization and ECM remodeling, and decreased MMP/TIMP expression. Fluoxetine also suppressed inflammatory responses in lung tissue and inhibited the expression of the inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein (MCP-1) and intercellular adhesion molecule-1 (ICAM-1). Conclusion: Fluoxetine inhibited MCT-induced ECM remodeling of the pulmonary artery and inflammation of lung tissue. These effects were related to its inhibition on MMPs/TIMPs and cytokine productions.Keywords: extracellular matrix; inflammation; pulmonary arterial hypertension; selective serotonin reuptake inhibitor Acta Pharmacologica Sinica (2011) 32: 217-222; doi: 10.1038/aps.2010 published online 10 Jan 2011 Original Article * To whom correspondence should be addressed. [11,12] . It was reported that the plasma concentration in serotonin was significantly increased in PAH patients [13] . We have previously reported that serotonin induced PASMCs mitogenesis in vitro, and serotonin selective reuptake inhibitor (SSRI) fluoxetine inhibited serotonininduced PASMCs proliferation via blocking SERT [14] . We have also found that SSRI fluoxetine and sertraline protected against pulmonary vascular remodeling by inhibiting pulmonary vascular muscularization in monocrotaline (MCT)-induced pulmonary hypertensive rats [15,16] . However, whether SSRI has a protective effect against ECM remodeling in the pulmonary artery remains unknown.Inflammatory mechanisms play an important role in the development of PAH. It has been demonstrated that lymphocytes and macrophages were present in the vicinity of remodeled pulmonary vessels and that cytokines such as interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) were increased in PAH patients [17][18][19][20] . We have also reported previously that chronic lung inflammation existed in MCT-induced PAH rats [21] . However, several studies have shown that...

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“…Via the 5-HT2A receptor eosinophil recruitment, airway inflammation, airway hyperresponsiveness, and remodeling is mediated in allergic asthma (79–81). In 2013, Kang et al showed that serotonin induces eosinophil trafficking and recruitment via activation of ROCK, MAPK, PI3K, and the PKC-calmodulin pathway (78).…”

Section: Serotonin Effects On Immune Cellsmentioning

confidence: 99%

The Effects of Serotonin in Immune Cells

Herr

Bode

Duerschmied

2017

Front. Cardiovasc. Med.

355

298

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Serotonin [5-hydroxytryptamine (5-HT)] plays an important role in many organs as a peripheral hormone. Most of the body’s serotonin is circulating in the bloodstream, transported by blood platelets and is released upon activation. The functions of serotonin are mediated by members of the 7 known mammalian serotonin receptor subtype classes (15 known subtypes), the serotonin transporter (SERT), and by covalent binding of serotonin to different effector proteins. Almost all immune cells express at least one serotonin component. In recent years, a number of immunoregulatory functions have been ascribed to serotonin. In monocytes/macrophages, for example, serotonin modulates cytokine secretion. Serotonin can also suppress the release of tumor necrosis factor-α and interleukin-1β by activating serotonin receptors. Furthermore, neutrophil recruitment and T-cell activation can both be mediated by serotonin. These are only a few of the known immunomodulatory roles of serotonin that we will review here.

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Interference of methysergide, a specific 5‐hydroxytryptamine receptor antagonist, with airway chronic allergic inflammation and remodelling in a murine model of asthma

Abstract: Serotonin may contribute to the development and maintenance of remodelling through the release of cytokines and of fibrogenic mediators. Serotonin should therefore be considered as relevant for the development and maintenance of airway remodelling.

Cited by 31 publications

References 68 publications

C-027 Inhibits IgE-mediated passive sensitization bronchoconstriction and acts as a histamine and serotonin antagonist in human airways

C-027 Inhibits IgE-mediated passive sensitization bronchoconstriction and acts as a histamine and serotonin antagonist in human airways

Fluoxetine inhibited extracellular matrix of pulmonary artery and inflammation of lungs in monocrotaline-treated rats

The Effects of Serotonin in Immune Cells

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