Sputum neurokinin A in Egyptian asthmatic children and adolescents: relation to exacerbation severity

Mostafa, Gehan Ahmed; Reda, Shereen M.; El-Aziz, M. M. Abd; Ahmed, Samar

doi:10.1111/j.1398-9995.2008.01784.x

Cited by 23 publications

(19 citation statements)

References 13 publications

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“…More conventional drug discovery efforts, beyond “electroceuticals”, have been inspired by observations such as outgrowth of sensory nerves and increased neuropeptide levels in a number of pathologic inflammatory diseases [247–249] For example, neurokinin receptor (NKr) antagonists have been tested clinically based on encouraging results in multiple animal models. These compounds have demonstrated efficacy in the treatment of emesis and depression, but their use in other areas, particularly in respiratory diseases has been mostly disappointing.…”

Section: Therapeutic Targeting Of Neuro-immune Interactionsmentioning

confidence: 99%

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

Ordovás-Montañés

Rakoff-Nahoum

Huang

et al. 2015

Trends in Immunology

149

123

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The nervous system and the immune system are the principal sensory interfaces between the internal and external environment. They are responsible for recognizing, integrating, and responding to varied stimuli, and have the capacity to form memories of these encounters leading to learned or ‘adaptive’ future responses. Here, we review the current understanding of the cross-regulation between these systems. The autonomic and somatosensory nervous systems regulate both the development and deployment of immune cells, with broad functions that impact hematopoiesis as well as priming, migration and cytokine production. In turn, specific immune cell subsets contribute to homeostatic neural circuits such as those controlling metabolism, hypertension and the inflammatory reflex. We examine the contribution of the somatosensory system to autoimmune, autoinflammatory, allergic, and infectious processes in barrier tissues and in this context, discuss opportunities for therapeutic manipulation of neuro-immune interactions.

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Section: Therapeutic Targeting Of Neuro-immune Interactionsmentioning

confidence: 99%

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

Ordovás-Montañés

Rakoff-Nahoum

Huang

et al. 2015

Trends in Immunology

149

123

View full text Add to dashboard Cite

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“…It was demonstrated that they are located in the excitatory nonadrenergic and noncholinergic nerves of the mammalian respiratory tract (12,13). Therefore, release of tachykinins by the excitation of these nerve systems is thought to be involved in the pathogenesis of airway allergy in humans (14,15). Because those factors are produced in the airway tissues during inflammatory responses, developing therapy that blocks the tachykinin-dependent signaling cascade might be beneficial for the treatment of allergic inflammation (16)(17)(18).…”

mentioning

confidence: 99%

“…Recent articles indicated that SP regulates the function of various leukocytes, such as vascular endothelial growth factor secretion from mast cells (19), cytotoxicity of NK cells (20), cytokine production by monocytes and T cells (21,22), induction of chemokine or chemokine receptor of macrophages (23,24), and Ag presentation of dendritic cells (DCs) (25). In contrast, NKA is known to control various vital responses, such as airway contraction, vasodilatation, and vascular permeability, in humans (15,16,26). However, the function of NKA in the immune system is less-well defined compared with the role of SP.…”

mentioning

confidence: 99%

Neuropeptide Signaling Activates Dendritic Cell-Mediated Type 1 Immune Responses through Neurokinin-2 Receptor

Kitamura

Kobayashi

Wakita

et al. 2012

The Journal of Immunology

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Neurokinin A (NKA), a neurotransmitter distributed in the central and peripheral nervous system, strictly controls vital responses, such as airway contraction, by intracellular signaling through neurokinin-2 receptor (NK2R). However, the function of NKA–NK2R signaling on involvement in immune responses is less-well defined. We demonstrate that NK2R-mediated neuropeptide signaling activates dendritic cell (DC)-mediated type 1 immune responses. IFN-γ stimulation significantly induced NK2R mRNA and remarkably enhanced surface protein expression levels of bone marrow-derived DCs. In addition, the DC-mediated NKA production level was significantly elevated after IFN-γ stimulation in vivo and in vitro. We found that NKA treatment induced type 1 IFN mRNA expressions in DCs. Transduction of NK2R into DCs augmented the expression level of surface MHC class II and promoted Ag-specific IL-2 production by CD4+ T cells after NKA stimulation. Furthermore, blockade of NK2R by an antagonist significantly suppressed IFN-γ production by both CD4+ T and CD8+ T cells stimulated with the Ag-loaded DCs. Finally, we confirmed that stimulation with IFN-γ or TLR3 ligand (polyinosinic-polycytidylic acid) significantly induced both NK2R mRNA and surface protein expression of human PBMC-derived DCs, as well as enhanced human TAC1 mRNA, which encodes NKA and Substance P. Thus, these findings indicate that NK2R-dependent neuropeptide signaling regulates Ag-specific T cell responses via activation of DC function, suggesting that the NKA–NK2R cascade would be a promising target in chronic inflammation caused by excessive type 1-dominant immunity.

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“…Moreover, recent studies showed that asthmatic subjects have increased concentrations of nonkinase plasminogen activator and plasminogen activator inhibitor [23] compared to controls and Neurokinin A significantly raises during exacerbations [24]. Interleukin-8 (IL-8) is a neutrophil chemoattractant which has been shown to be increased during asthma exacerbations [25] and in patients with severe persistent asthma [17], suggesting a role for monitoring asthma exacerbations and assessing the effectiveness of a medication in severe asthmatics.…”

Section: Fluid-phase Mediatorsmentioning

confidence: 99%

Markers of airway inflammation in pulmonary diseases assessed by induced sputum

Dragonieri

Tongoussouva

Zanini

et al. 2016

Monaldi Arch Chest Dis

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During recent years there has been a growing interest in using non-invasive biomarkers to understand and monitor the airway inflammation in subjects with respiratory tract disorders. To date, the best validated and performing non-invasive biomarkers are measures of inflammation in induced sputum in both cellular and fluid phase, which can provide biological insights into the pathogenesis of respiratory diseases such as asthma and chronic obstructive pulmonary disease. The purpose of this review is to examine the principal literature on the different markers of inflammation in pulmonary diseases assessed by induced sputum analysis in either cellular or fluid phase.

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Sputum neurokinin A in Egyptian asthmatic children and adolescents: relation to exacerbation severity

Abstract: Sputum NKA is up-regulated during acute asthma exacerbation and it positively correlates to its severity. Thus, NKA may aid in objective classification of the exacerbation severity. In addition, NKA may be a target for new asthma therapy.

Cited by 23 publications

References 13 publications

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

Neuropeptide Signaling Activates Dendritic Cell-Mediated Type 1 Immune Responses through Neurokinin-2 Receptor

Markers of airway inflammation in pulmonary diseases assessed by induced sputum

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