Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs

Cardenas, Silvia; Scuri, Mario; Samsell, Lennie; Ducatman, Barbara S.; Bejarano, P.A.; Auais, Alexander; Doud, Melissa; Mathee, Kalai; Piedimonte, Giovanni

doi:10.1152/ajplung.00017.2010

Cited by 8 publications

(21 citation statements)

References 47 publications

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“…K252a has been shown to inhibit NGF receptor trkA, trkB, and trkC phosphorylation (26) and block NGF-induced neuropeptide production (7,36). Also, NGF antibody has been shown to inhibit enhanced airway innervation after irritant exposures (5,16). To ensure sufficient reduction of NGF effects, the mice were treated using both aerosol exposure and subcutaneous injection.…”

Section: Methodsmentioning

confidence: 99%

“…To ensure sufficient reduction of NGF effects, the mice were treated using both aerosol exposure and subcutaneous injection. The final dosages of K252a and NGF antibody were based on previous studies (4,5,7,36) and our preliminary data. The final concentration of K252a for the aerosol exposure (Sigma-Aldrich, St. Louis, MO) was 100 nM, and 100 g/kg of K252a were subcutaneously injected.…”

Section: Methodsmentioning

confidence: 99%

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Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung

Benders

Hunter

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Wu ZX, Benders KB, Hunter DD, Dey RD. Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung. Am J Physiol Lung Cell Mol Physiol 302: L152-L159, 2012. First published October, 14, 2011 doi:10.1152/ajplung.00071.2011.-Our recent study showed that prenatal and early postnatal exposure of mice to sidesteam tobacco smoke (SS), a surrogate to environmental tobacco smoke (ETS), leads to increased airway responsiveness and sensory innervation later in life. However, the underlying mechanism initiated in early life that affects airway responses later in life remains undefined. The concomitant increase in nerve growth factor (NGF) after exposures suggests that NGF may be involved the regulation of airway innervation. Since NGF regulates sympathetic nerve responses, as well as sensory nerves, we extended previous studies by examining neuropeptide Y (NPY), a neuropeptide associated with sympathetic nerves. Different age groups of mice, postnatal day (PD) 2 and PD21, were exposed to either SS or filtered air (FA) for 10 consecutive days. The level of NPY protein in lung and the density of NPY nerve fibers in tracheal smooth muscle were significantly increased in the PD2-11SS exposure group compared with PD2-11FA exposure. At the same time, the level of NGF in lung tissue was significantly elevated in the PD2-11SS exposure groups. However, neither NPY (protein or nerves) nor NGF levels were significantly altered in PD21-30SS exposure group compared with the PD21-30FA exposure group. Furthermore, pretreatment with NGF antibody or K252a, which inhibits a key enzyme (tyrosine kinase) in the transduction pathway for NGF receptor binding, significantly diminished SS-enhanced NPY tracheal smooth muscle innervation and the increase in methacholine-induced airway resistance. These findings show that SS exposure in early life increases NPY tracheal innervation and alters pulmonary function and that these changes are mediated through the NGF. airway innervation; asthma; secondhand smoke; neurotrophic factor ENVIRONMENTAL TOBACCO SMOKE (ETS) is an environmental trigger factor that leads to airway inflammation and asthma symptoms in susceptible individuals and animals (25,33,34). Exposure to ETS in utero or during early postnatal development increases the incidence of respiratory illnesses (11,13,28,31,35) later in life. Epidemiological studies (11,13,25,28,(32)(33)(34)(35) show that the probability of developing or exacerbating childhood asthma increases in children of mothers who smoke cigarettes. These results suggest that the prenatal and early postnatal periods are critical periods of developmental sensitivity to cigarette smoke exposure. Indeed, our recent study (40) showed that exposure to side-steam tobacco smoke (SS) during prenatal and early postnatal life produces changes in lung function and airway innervation later in life, supporting the concept of an early life critical period of susceptibility. However, the underlying mechanism initiated by early life exposures that affect lung st...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung

Benders

Hunter

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

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“…However, the functional role of neurotrophins in the airway are still under investigation. Here, recent data suggest that NGF is released by airway nerves in response to irritants [e.g., ozone (120,322) or cigarette smoke (336)], allergens (346), and infectious agents (38) contributing to irritability and enhanced contractility. NGF can also be derived from airway epithelial cells, for example following viral or bacterial infections (38,222).…”

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

“…Here, recent data suggest that NGF is released by airway nerves in response to irritants [e.g., ozone (120,322) or cigarette smoke (336)], allergens (346), and infectious agents (38) contributing to irritability and enhanced contractility. NGF can also be derived from airway epithelial cells, for example following viral or bacterial infections (38,222). The presumed target of the released NGF is ASM, given expression of the cognate TrkA receptors in ASM (75,213,222,238).…”

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

“…Finally, the effects of inflammation (321,332), infection (124), pollutants (252), and other stimuli on airway nerves are being explored, again with the intent of suppressing excessive bronchoconstriction, as well as cough reflexes. Here, an emerging theme is again neurotrophins such as NGF, BDNF, and glial-derived neurotrophic factor that serve to influence airway reactivity (175,176,200) as well as enhance immunity and reactivity in the airway following bacterial infections (38), exposure to house dust mite (and important aspect of allergic asthma) (346), allergen challenge (176), or ozone (322). Furthermore, it may be relevant to consider whether novel mechanisms such as TAS2R and OGR1 are present and functional in neural pathways involved in airway tone.…”

Section: Neural Controlmentioning

confidence: 99%

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Airway smooth muscle in airway reactivity and remodeling: what have we learned?

Prakash

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

179

154

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Prakash YS. Airway smooth muscle in airway reactivity and remodeling: what have we learned? Am J Physiol Lung Cell Mol Physiol 305: L912-L933, 2013. First published October 18, 2013 doi:10.1152/ajplung.00259.2013.-It is now established that airway smooth muscle (ASM) has roles in determining airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are central to the manifestation of allergic, inflammatory, and fibrotic airway diseases in both children and adults, as well as to airway responses to local and environmental exposures. Emerging evidence points to novel signaling mechanisms within ASM cells of different species that serve to control diverse features, including 1) [Ca 2ϩ ]i contractility and relaxation, 2) cell proliferation and apoptosis, 3) production and modulation of extracellular components, and 4) release of pro-vs. anti-inflammatory mediators and factors that regulate immunity as well as the function of other airway cell types, such as epithelium, fibroblasts, and nerves. These diverse effects of ASM "activity" result in modulation of bronchoconstriction vs. bronchodilation relevant to airway hyperresponsiveness, airway thickening, and fibrosis that influence compliance. This perspective highlights recent discoveries that reveal the central role of ASM in this regard and helps set the stage for future research toward understanding the pathways regulating ASM and, in turn, the influence of ASM on airway structure and function. Such exploration is key to development of novel therapeutic strategies that influence the pathophysiology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis.

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Down-Regulation of Nerve Growth Factor Expression in the Bladder by Antisense Oligonucleotides as New Treatment for Overactive Bladder

et al. 2013

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Purpose Nerve growth factor over expression in the bladder has a role in overactive bladder symptoms via the mediation of functional changes in bladder afferent pathways. We studied whether blocking nerve growth factor over expression in bladder urothelium by a sequence specific gene silencing mechanism would suppress bladder overactivity and chemokine expression induced by acetic acid. Materials and Methods Female Sprague-Dawley® rats anesthetized with isoflurane were instilled with 0.5 ml saline, scrambled or TYE™ 563 labeled antisense oligonucleotide targeting nerve growth factor (12 μM) alone or complexed with cationic liposomes for 30 minutes. The efficacy of nerve growth factor antisense treatments for acetic acid induced bladder overactivity was assessed by cystometry. Bladder nerve growth factor expression levels and cellular distribution were quantified by immunofluorescence staining and enzyme-linked immunosorbent assay. Effects on bladder chemokine expression were measured by Luminex® xMAP® analysis. Results Liposomes were needed for bladder uptake of oligonucleotide, as seen by the absence of bright red TYE 563 fluorescence in rats instilled with oligonucleotide alone. At 24 hours after liposome-oligonucleotide treatment baseline bladder activity during saline infusion was indistinct in the sham and antisense treated groups with a mean ± SEM intercontraction interval of 348 ± 55 and 390 ± 120 seconds, respectively. Acetic acid induced bladder overactivity was shown by a decrease in the intercontraction interval to a mean of 33.2% ± 4.0% of baseline in sham treated rats. However, the reduction was blunted to a mean of 75.8% ± 3.4% of baseline in rats treated with liposomal antisense oligonucleotide (p <0.05). Acetic acid induced increased nerve growth factor in the urothelium of sham treated rats, which was decreased by antisense treatment, as shown by enzyme-linked immunosorbent assay and reduced nerve growth factor immunoreactivity in the urothelium. Increased nerve growth factor in bladder tissue was associated with sICAM-1, sE-selectin, CXCL-10 and 1, leptin, MCP-1 and vascular endothelial growth factor over expression, which was significantly decreased by nerve growth factor antisense treatment (p <0.01). Conclusions Acetic acid induced bladder overactivity is associated with nerve growth factor over expression in the urothelium and with chemokine up-regulation. Treatment with liposomal antisense suppresses bladder overactivity, and nerve growth factor and chemokine expression. Local suppression of nerve growth factor in the bladder could be an attractive approach for overactive bladder. It would avoid the systemic side effects that may be associated with nonspecific blockade of nerve growth factor expression.

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Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs

Cited by 8 publications

References 47 publications

Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung

Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

Down-Regulation of Nerve Growth Factor Expression in the Bladder by Antisense Oligonucleotides as New Treatment for Overactive Bladder

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