vasoactive-intestinal-peptide and Rhinitis--Allergic

Allergic rhinitis (AR) is a very common disease with a high prevalence worldwide. It is an IgE-mediated type 2 inflammatory disease following exposure to inhalant allergens. A multitude of different neuropeptides including substance P, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), and neuromedin U (NMU) can be released via peripheral axon or central reflexes, interact with immune cells, and thus contribute to neurogenic inflammation which causes the nasal hyperreactivity (NHR) characteristic of AR. Independent production of neuroendocrine hormones and neuropeptides by immune cells has also been demonstrated. Neuro-immune cell units arise when immune and neuronal cells colocalize, for which typical anatomic regions are, e.g., the mast cell-nerve functional unit. The focus of this review is the elucidation of neuroimmune communication mechanisms in AR.. Die allergische Rhinitis (AR) ist eine sehr häufige Erkrankung mit weltweit hoher Prävalenz. Sie ist eine IgE-vermittelte und entzündungsbedingte Typ-2-Erkrankung nach Exposition gegenüber inhalativen Allergenen. Eine Vielzahl von Neuropeptiden wie Substanz P (SP), vasoaktives intestinales Peptid (VIP), „calcitonin gene-related peptide“ (CGRP), Nervenwachstumsfaktor (NGF) und Neuromedin U (NMU) können über periphere Axonreflexe oder zentrale Reflexe freigesetzt werden, mit Immunzellen interagieren und sind so an einer neurogenen Entzündung beteiligt, die zur nasalen Hyperreaktivität (NHR) der AR führt. Die eigenständige Produktion von neuroendokrinen Hormonen und Neuropeptiden durch Immunzellen wurde ebenfalls nachgewiesen. Neuroimmunzellverbände entstehen, wenn Immun- und neuronale Zellen kolokalisieren. Typische anatomische Regionen dafür sind beispielsweise die Nerv-Mastzellen-Einheit. In dieser Übersicht liegt der Fokus auf der Ausarbeitung neuroimmunologischer Kommunikationsmechanismen der AR.

Topics: Calcitonin Gene-Related Peptide; Humans; Nasal Mucosa; Neuroimmunomodulation; Neuropeptides; Rhinitis, Allergic; Vasoactive Intestinal Peptide

Topics: Adult; Geniculate Ganglion; Humans; Nasal Mucosa; Neurosurgical Procedures; Parasympathetic Nervous System; Rhinitis, Allergic; Temperature; Vasoactive Intestinal Peptide

Topics: Humans; Nasal Mucosa; Neuroimmunomodulation; Neuropeptides; Rhinitis, Allergic; Vasoactive Intestinal Peptide

We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation. Nasal provocation tests, ELISA, qRT-PCR, western blot, flow cytometry and chemotaxis assays in modified micro-Boyden chambers, were all used, to achieve our objectives. Herein we show that AR patients increased the amounts of VIP and PGD2 in their nasal secretions in the early phase reaction, however CRTH2 gene expression from leukocytes recovered in their nasal secretions was upregulated only during the late phase reaction. The TKIs; Genistein, Erbstatin and Herbimycin A, induced the gene expression of CRTH2 and increased the protein content of CRTH2 in both human lymphocytes and eosinophils. This was functional as PGD2/VIP-induced eosinophil chemotaxis was augmented by the TKIs and inhibited by pervanadate, the tyrosine phosphatase inhibitor. These results open channels for therapeutic modalities targeting CRTH2 molecules in AR.

Topics: Adult; Antigens, Dermatophagoides; Cell Movement; Cells, Cultured; Eosinophils; Female; Gene Expression Regulation; Genistein; Humans; Hydroquinones; Lymphocytes; Male; Nasal Mucosa; Neuroimmunomodulation; Prostaglandin D2; Protein Kinase Inhibitors; Receptors, Immunologic; Receptors, Prostaglandin; Rhinitis, Allergic; Rifabutin; Vasoactive Intestinal Peptide

To explore the expression and significance of vasoactive intestinal peptide and Pituitary adenylate cyclase activiting polypeptide (VIP/PACAP) of nasal mucosa in rats with allergic rhinitis (AR), and the function of botulinum toxin-A(BTX-A) to inhibit the expression of VIP/PACAP in AR.. Thirty Sprague-Dawley rats were randomly divided into 3 groups, which were the AR group, the intervention group, and the control group. In the AR group, ovalbumin was used to sensitize healthy rats. In the intervention group, BTX-A was dripped into the nasal cavity of AR rats 7 times. In the control group, only physiological saline was used to drip into the nasal cavity of AR rats. Changes of the rats' behavior were observed. ELISA were used to detected the concentration variation of serum IFN-γ and IL-4. Histopathology and immunohistochemistry were employed to observe morphology in the rats' nasal mucosal and the expression of VIP/PACAP. Statistical analysis was also made.. (1)The typical symptoms marks of nasal scratching, sneezing, nasal blockage and rhinorrhea of AR group (7.5 ± 0.50) were higher than intervention group (1 ± 0.27) and control group (0.8 ± 0.31). (2) Comparing to intervention group and control group, the serm IFN-γ of the AR group obvious reduced (P < 0.05), the serm IL-4 of the AR group obvious rose (P < 0.01), and the serm Th1/Th2 (IFN-γ/IL-4) of the AR group obvious reduced (P < 0.01). (3) Comparing to intervention group and control group, the cilium loss, inflammatory cells infiltration, and inflammatory cells exudation of nasal mucosa in AR group were more obviously (P < 0.01), and the intervention group of the 3 indexes was obviously than control group. (4) The expression of VIP in the rats' nasal mucosa of the AR group (13.27 ± 2.74) were more intense than intervention group (5.21 ± 2.18) and control group (3.56 ± 5.30) (P < 0.01), and the expression of PACAP in the rats' nasal mucosa of the AR group (20.97 ± 2.14) were more intense than intervention group (6.33 ± 3.04) and control group (4.63 ± 1.25) (P < 0.01). (5) In all the 3 groups, there was positive correlation between expression of negative in VIP/PACAP and Thl/Th2 cell infiltration(r were respectively -0.340 and -0.223, P < 0.05).. The VIP/PACAP in the rats' nasal mucosa may play an important role in pathogenesis of AR, and BTX-A could improve the symptoms of AR through inhibition of the expression of VIP/ PACAP.

Topics: Animals; Botulinum Toxins, Type A; Disease Models, Animal; Interferon-gamma; Interleukin-4; Nasal Mucosa; Ovalbumin; Paranasal Sinuses; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Vasoactive Intestinal Peptide

Anticholinergic drugs or vidian neurectomy can alleviate the symptoms of allergic rhinitis.. To show that inhibition of the cholinergic nerve influences the balance of T-helper type 1 and 2 cells in allergic rhinitis mice.. Twenty-four mice were randomly allocated to 1 of 4 groups: control, model, model with ipratropium bromide treatment, and model with 6-hydroxydopamine treatment. Allergic model-treated mice were sensitized with ovalbumin. Evaluation of allergic symptoms was recorded according to a symptom score. Ovalbumin serum IgE was measured by enzyme-linked immunosorbent assay. Expression of interleukin-4, interferon-γ, forkhead box P3, substance P, and vasoactive intestinal peptides was detected by immunohistochemistry and imaging analysis.. Symptoms in allergic mice were significantly alleviated by ipratropium bromide. Ovalbumin serum IgE and eosinophils of nasal mucosa were significantly decreased. Interleukin-4 expression level was significantly higher in the allergic model group than in the control group and significantly decreased by ipratropium bromide (P < .05). In contrast, the expression of forkhead box P3 was lower in the allergic model group than in the control group and increased with treatment by ipratropium bromide (P < .05). Conversely, interferon-γ expression was not changed by anticholinergic treatment in the nasal mucosa of allergic mice. Expression of substance P and vasoactive intestinal peptide was significantly increased in allergic mice and decreased by ipratropium bromide. Sympathetic denervation did not change the expression of interleukin-4, interferon-γ, forkhead box P3, substance P, and vasoactive intestinal peptide.. inhibition of the cholinergic nerve not only alleviated symptoms of allergic rhinitis by inhibiting the impulse of the parasympathetic nerve but also modulated the T-helper type 2-predominant immune reaction, expression of neuropeptides, and related inflammation factors.

Topics: Adrenergic Agents; Animals; Cholinergic Antagonists; Cholinergic Neurons; Disease Models, Animal; Eosinophils; Female; Forkhead Transcription Factors; Gene Expression; Immunoglobulin E; Interferon-gamma; Interleukin-4; Ipratropium; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Oxidopamine; Parasympathetic Nervous System; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Substance P; Th1 Cells; Th1-Th2 Balance; Th2 Cells; Vasoactive Intestinal Peptide