Dataset Information

An advanced recording and analysis system for the differentiation of guinea pig cough responses to citric acid and prostaglandin E2 in real time.

ABSTRACT: Cough number and/or sound have been used to assess cough sensitivity/intensity and to discriminate cough patterns in clinical settings. However, to date, only manual counting of cough number in an offline manner is applied in animal cough studies, which diminishes the efficiency of cough identification and hinders the diagnostic discrimination of cough patterns, especially in animals with pulmonary diseases. This study aims to validate a novel recording/analysis system by which cough numbers are automatically counted and cough patterns are comprehensively differentiated in real time. The experiment was carried out in conscious guinea pigs exposed to aerosolized citric acid (CA, 150 mM) and prostaglandin E2 (PGE2, 0.43 mM). Animal body posture (video), respiratory flow, and cough acoustics (audio) were simultaneously monitored and recorded. Cough number was counted automatically, and cough sound parameters including waveform, duration, power spectral density, spectrogram, and intensity, were analyzed in real time. Our results showed that CA- and PGE2-evoked coughs had the same cough numbers but completely different patterns [individual coughs vs. bout(s) of coughs]. Compared to CA-evoked coughs, PGE2-evoked coughs possess a longer latency, higher cough rate (coughs/min), shorter cough sound duration, lower cough sound intensity, and distinct cough waveforms and spectrograms. A few mucus- and wheeze-like coughs were noted in response to CA but not to PGE2. In conclusion, our recording/analysis system is capable of automatically counting the cough number and successfully differentiating the cough pattern by using valuable cough sound indexes in real time. Our system enhances the objectivity, accuracy, and efficiency of cough identification and count, improves the intensity evaluation, and offers ability for pattern discrimination compared to traditional types of cough identification. Importantly, this approach is beneficial for assessing the efficacy of putative antitussive drugs in animals without or with pulmonary diseases, particularly in cases without significant change in cough number.

SUBMITTER: Zhuang J

PROVIDER: S-EPMC6530870 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An advanced recording and analysis system for the differentiation of guinea pig cough responses to citric acid and prostaglandin E2 in real time.

Zhuang Jianguo J Zhao Lei L Gao Xiuping X Xu Fadi F

PloS one 20190522 5

Cough number and/or sound have been used to assess cough sensitivity/intensity and to discriminate cough patterns in clinical settings. However, to date, only manual counting of cough number in an offline manner is applied in animal cough studies, which diminishes the efficiency of cough identification and hinders the diagnostic discrimination of cough patterns, especially in animals with pulmonary diseases. This study aims to validate a novel recording/analysis system by which cough numbers are ...[more]

PMID: 31116792

Similar Datasets

Project description:Inflammatory dendritic cells (DCs) are a distinct subset of DCs that derive from circulating monocytes infiltrating injured tissues. Monocytes can differentiate into DCs with different functional signatures, depending on the presence of environment stimuli. Among these stimuli, transforming growth factor-beta (TGF-β) and prostaglandin E2 (PGE2) have been shown to modulate the differentiation of monocytes into DCs with different phenotypes and functional profiles. In fact, both mediators lead to contrasting outcomes regarding the production of inflammatory and anti-inflammatory cytokines. Previously, we have shown that human semen, which contains high concentrations of PGE2, promoted the differentiation of DCs into a tolerogenic profile through a mechanism dependent on signaling by E-prostanoid receptors 2 and 4. Notably, this effect was induced despite the huge concentration of TGF-β present in semen, suggesting that PGE2 overrides the influence exerted by TGF-β. No previous studies have analyzed the joint actions induced by PGE2 and TGF-β on the function of monocytes or DCs. Here, we analyzed the phenotype and functional profile of monocyte-derived DCs differentiated in the presence of TGF-β and PGE2. DC differentiation guided by TGF-β alone enhanced the expression of CD1a and abrogated LPS-induced expression of IL-10, while differentiation in the presence of PGE2 impaired CD1a expression, preserved CD14 expression, abrogated IL-12 and IL-23 production, stimulated IL-10 production, and promoted the expansion of FoxP3+ regulatory T cells in a mixed lymphocyte reaction. Interestingly, DCs differentiated in the presence of TGF-β and PGE2 showed a phenotype and functional profile closely resembling those induced by PGE2 alone. Finally, we found that PGE2 inhibited TGF-β signaling through an action exerted by EP2 and EP4 receptors coupled to cyclic AMP increase and protein kinase A activity. These results indicate that PGE2 suppresses the influence exerted by TGF-β during DC differentiation, imprinting a tolerogenic signature. High concentrations of TGF-β and PGE2 are usually found in infectious, autoimmune, and neoplastic diseases. Our observations suggest that in these scenarios PGE2 might play a mandatory role in the acquisition of a regulatory profile by DCs.

Project description:IntroductionIdiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with very few effective treatments. The key effector cells in fibrosis are believed to be fibroblasts, which differentiate to a contractile myofibroblast phenotype with enhanced capacity to proliferate and produce extracellular matrix. The role of the lung epithelium in fibrosis is unclear. While there is evidence that the epithelium is disrupted in IPF, it is not known whether this is a cause or a result of the fibroblast pathology. We hypothesized that healthy epithelial cells are required to maintain normal lung homeostasis and can inhibit the activation and differentiation of lung fibroblasts to the myofibroblast phenotype. To investigate this hypothesis, we employed a novel co-culture model with primary human lung epithelial cells and fibroblasts to investigate whether epithelial cells inhibit myofibroblast differentiation.Measurements and main resultsIn the presence of transforming growth factor (TGF)-β, fibroblasts co-cultured with epithelial cells expressed significantly less α-smooth muscle actin and collagen and showed marked reduction in cell migration, collagen gel contraction, and cell proliferation compared to fibroblasts grown without epithelial cells. Epithelial cells from non-matching tissue origins were capable of inhibiting TGF-β induced myofibroblast differentiation in lung, keloid and Graves' orbital fibroblasts. TGF-β promoted production of prostaglandin (PG) E2 in lung epithelial cells, and a PGE2 neutralizing antibody blocked the protective effect of epithelial cell co-culture.ConclusionsWe provide the first direct experimental evidence that lung epithelial cells inhibit TGF-β induced myofibroblast differentiation and pro-fibrotic phenotypes in fibroblasts. This effect is not restricted by tissue origin, and is mediated, at least in part, by PGE2. Our data support the hypothesis that the epithelium plays a crucial role in maintaining lung homeostasis, and that damaged and/ or dysfunctional epithelium contributes to the development of fibrosis.

Project description:Interactions between adipocytes and macrophages are associated with metabolic disorders. Production of pro-inflammatory mediators and the release of free fatty acids (FFAs) increase when these cells are co-cultured; butyrate significantly diminishes these effects by suppressing both the macrophage inflammatory and adipocyte lipolysis pathways. Butyrate is known to up-regulate the expression of prostaglandin E2 (PGE2). Therefore, we hypothesized that PGE2 is associated with the suppression of lipolysis by butyrate in co-culture.Using contact or transwell co-culture methods with differentiated 3T3-L1 adipocytes and RAW264.7 macrophages, we investigated the effects of butyrate on the release of PGE2 into the medium and on lipolysis in adipocytes. To elucidate the underlying mechanism, we examined the effects of butyrate on cyclooxygenase-2 (COX2) and phospholipase A2 (PLA2) in co-cultured cells, and cyclic adenine monophosphate (cAMP) and protein kinase A type 1-? regulatory subunit (PRKAR1A) in co-cultured adipocytes. Silent interfering (si)RNA targeting of G-protein-coupled receptor (GPR)41 and 109A was employed to examine the effect on lipolysis in TNF-?-stimulated adipocytes.Co-culture increased PGE2 release into the medium, compared with cells cultured separately. Butyrate significantly increased PGE2 production. Co-culture elevated COX2 expression in macrophages and adipocytes, and butyrate further enhanced this effect. Co-culture enhanced cytosolic PLA2 activity in macrophages, which was further enhanced by butyrate. As for lipolysis, co-culture increased the release of FFAs and free glycerol into the medium, whereas butyrate (and to a lesser extent, PGE2) suppressed FFAs and free glycerol release. An inhibition study using a prostaglandin E receptor 3-selective antagonist suggested that approximately 40% of the suppressive effect of butyrate depends on the PGE2-mediated pathway, whereas 60% depends on a non-PGE2-mediated pathway. Co-culture increased cAMP and PRKAR1A levels in adipocytes, whereas butyrate restored the levels to those of the control. Similarly, in TNF-?-stimulated adipocytes, butyrate reduced FFAs and free glycerol release. siRNA inhibition of GPR41 and GPR109A suggested that the GPR109A-mediated pathway predominates, but the GPR41-mediated pathway also regulates the effect of butyrate on lipolysis in TNF-?-stimulated 3T3-L1 cells.Butyrate attenuates lipolysis in adipocytes co-cultured with macrophages via non-PGE2-mediated and PGE2-mediated pathways.

Dataset Information

An advanced recording and analysis system for the differentiation of guinea pig cough responses to citric acid and prostaglandin E2 in real time.

Publications

An advanced recording and analysis system for the differentiation of guinea pig cough responses to citric acid and prostaglandin E2 in real time.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets