Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of studies have implicated severe infections early in life as a risk factor for the subsequent development of asthma. In particular it has been suggested that respiratory syncytial virus (RSV) infection may enhance the development of "allergic" inflammatory responses when the host is exposed to allergens after an episode of bronchiolitis. It has also been suggested that neuronal mechanisms are important in RSV infection and subsequent airway hyperreactivity. Recently we advanced the hypothesis that immune and neuronal mechanisms may be linked and that combined neuroimmune responses may be in play. In the airways a dense network of sensory nerve fibers is strategically placed just below the epithelial surface so that any change in the bronchial environment may stimulate the release of the proinflammatory neuropeptide substance P. During RSV infection, stimulation of these nerves causes a marked increase in airway vascular permeability over that in pathogen-free rats and results in an increase in overall inflammatory status. Our work has revealed that these changes are mediated by the high affinity receptor for substance P [neurokinin (NK) 1 receptor], the expression of which is greatly increased by RSV. This up-regulation presumably occurs at the gene expression level, as NK1 receptor mRNA levels increase substantially during RSV infection. We have also shown that T lymphocyte subpopulations within the bronchial-associated lymphoid tissue in the lungs of RSV-infected rats express high levels of the NK1 receptor. As a consequence stimulation of the sensory nerves by any airborne irritant has the potential of causing a new inflammatory cycle mediated by NK1 receptor-expressing T lymphocytes attracted into the airways and activated by substance P. This mechanism may establish important neuroimmune interactions, which undergo long term dysregulation after RSV infection and predispose to airway inflammation and hyperreactivity. Finally our most recent studies show that RSV infection promotes a large increase in the expression of nerve growth factor (NGF) and neurotrophin receptors. RSV-induced release of NGF leads to short and long term changes in the distribution and reactivity of sensory nerves across the respiratory tract, participating to exaggerated inflammatory reactions during and after the infection. NGF and its receptors may also amplify other immunoinflammatory and neuronal pathways contributing to airway inflammation and hyperreactivity. On the basis of these observations, we postulate that changes of neurotrophin expression in the respiratory tract may represent an important link between early life viral infections and childhood asthma.
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PMID:Contribution of neuroimmune mechanisms to airway inflammation and remodeling during and after respiratory syncytial virus infection. 1267 55

Airway infections or irritant exposures during early postnatal periods may contribute to the onset of childhood asthma. The purpose of this study was to examine critical periods of postnatal airway development during which ozone (O(3)) exposure leads to heightened neural responses. Rats were exposed to O(3) (2 ppm) or filtered air for 1 hour on specific postnatal days (PDs) between PD1 and PD29, and killed 24 hours after exposure. In a second experiment, rats were exposed to O(3) on PD2-PD6, inside a proposed critical period of development, or on PD19-PD23, outside the critical period. Both groups were re-exposed to O(3) on PD28, and killed 24 hours later. Airways were removed, fixed, and prepared for substance P (SP) immunocytochemistry. SP nerve fiber density (NFD) in control extrapulmonary (EXP) epithelium/lamina propria (EPLP) increased threefold, from 1% to 3.3% from PD1-PD3 through PD13-PD15, and maintained through PD29. Upon O(3) exposure, SP-NFD in EXP-smooth muscle (SM) and intrapulmonary (INT)-SM increased at least twofold at PD1-PD3 through PD13-PD15 in comparison to air exposure. No change was observed at PD21-PD22 or PD28-PD29. In critical period studies, SP-NFD in the INT-SM and EXP-SM of the PD2-PD6 O(3) group re-exposed to O(3) on PD28 was significantly higher than that of the group exposed at PD19-PD23 and re-exposed at PD28. These findings suggest that O(3)-mediated changes in sensory innervation of SM are more responsive during earlier postnatal development. Enhanced responsiveness of airway sensory nerves may be a contributing mechanism of increased susceptibility to environmental exposures observed in human infants and children.
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PMID:Sensory neural responses to ozone exposure during early postnatal development in rat airways. 2011 20

Objectives. To assess the induced sputum substance P (ISSP) levels in children having difficult-to-treat asthma (DA) with and without gastroesophageal reflux (GER). We aimed also to evaluate the association of GER with childhood DA, relationship of GER severity with childhood asthma control test (C-ACT), FEV(1), peak expiratory flow (PEF) variability, and ISSP. Finally, we tried to evaluate esomeprazole treatment effect on C-ACT and FEV(1) in children with DA. Methods. Spirometry, C-ACT, upper gastrointestinal endoscopy, and ISSP measurement were done for children with DA compared to healthy controls. Results. ISSP was high in DA with higher levels in the group having associated GER. In the latter group, ISSP and C-ACT improved significantly after esomeprazole treatment while FEV(1) and PEF variability did not improve. Reflux severity was positively correlated with ISSP and negatively correlated with FEV(1). Conclusions. GER was found in 49% of our patients with childhood DA. Very high ISSP levels in children with DA may be used as a marker for presence of GERD. Esomeprazole therapy improved asthma symptoms but did not improve lung function.
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PMID:Induced Sputum Substance P in Children with Difficult-to-Treat Bronchial Asthma and Gastroesophageal Reflux: Effect of Esomeprazole Therapy. 2225 35