Tag: Human

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

Pulm Pharmacol Ther. 2016 Nov 2;:

Authors: Baldissera L, Squebola-Cola DM, Calixto MC, Lima-Barbosa AP, Rennó AL, Anhê GF, Condino-Neto A, De Nucci G, Antunes E

Abstract
OBJECTIVES: Activators of soluble guanylyl cyclase (sGC) act preferentially in conditions of enzyme oxidation or haem group removal. This study was designed to investigate the effects of the sGC activator BAY 60-2770 in murine airways inflammation and human eosinophil chemotaxis.
METHODS: C57Bl/6 mice treated or not with BAY 60-2770 (1 mg/kg/day, 14 days) were intranasally challenged with ovalbumin (OVA). At 48 h, bronchoalveolar lavage fluid (BALF) was performed, and circulating blood, bone marrow and lungs were obtained. Human eosinophils purified from peripheral blood were used to evaluate the cell chemotaxis.
RESULTS: OVA-challenge promoted marked increases in eosinophil number in BAL, lung tissue, circulating blood and bone marrow, all of which were significantly reduced by BAY 60-2770. The IL-4 and IL-5 levels in BALF were significantly reduced by BAY 60-2770. Increased protein expression of iNOS, along with decreases of expression of sGC (?1 and ?1 subunits) and cGMP levels were detected in lung tissue of OVA-challenged mice. BAY 60-2770 fully restored to baseline the iNOS and sGC subunit expressions, and cGMP levels. In human isolated eosinophils, BAY 60-2770 (1-5 ?M) had no effects on the cGMP levels and eotaxin-induced chemotaxis; however, prior incubation with ODQ (10 ?M) markedly elevated the BAY 60-2770-induced cyclic GMP production, further inhibiting the eosinophil chemotaxis.
CONCLUSIONS: BAY 60-2770 reduces airway eosinophilic inflammation and rescue the sGC levels. In human eosinophils under oxidized conditions, BAY 60-2770 elevates the cGMP levels causing cell chemotaxis inhibition. BAY 60-2770 may reveal a novel therapeutic target for asthma treatment.

PMID: 27816773 [PubMed – as supplied by publisher]

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Small airway-on-a-chip enables analysis of human COPD and asthma – News-Medical.net


Harvard School of Engineering and Applied Sciences

Small airway-on-a-chip enables analysis of human COPD and asthma
News-Medical.net
COPD and asthma are inflammatory reactions in the lung which can be dramatically exacerbated by viral and bacterial infections, as well as smoking. It is known that many of the associated disease processes occur in the conducting airway sections of the …
Small airway-on-a-chip improves study of human COPD and asthmaHarvard School of Engineering and Applied Sciences

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Small airway-on-a-chip improves study of human COPD and asthma – Harvard School of Engineering and Applied Sciences


Harvard School of Engineering and Applied Sciences

Small airway-on-a-chip improves study of human COPD and asthma
Harvard School of Engineering and Applied Sciences
A research team at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University leveraged its organ-on-a-chip technology to develop a model of the human …
Modeling COPD and asthma in a human small airway-on-a-chipMedical Xpress

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View full post on asthma – Google News

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Modeling COPD and asthma in a human small airway-on-a-chip – Medical Xpress


Medical Xpress

Modeling COPD and asthma in a human small airway-on-a-chip
Medical Xpress
COPD and asthma are inflammatory reactions in the lung which can be dramatically exacerbated by viral and bacterial infections, as well as smoking. It is known that many of the associated disease processes occur in the conducting airway sections of the …

and more »

View full post on asthma – Google News

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Modeling COPD and asthma in a human small airway-on-a-chip – EurekAlert (press release)

Modeling COPD and asthma in a human small airway-on-a-chip
EurekAlert (press release)
COPD and asthma are inflammatory reactions in the lung which can be dramatically exacerbated by viral and bacterial infections, as well as smoking. It is known that many of the associated disease processes occur in the conducting airway sections of the …

and more »

View full post on asthma – Google News

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A systems approach to understanding human rhinovirus and influenza virus infection.

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A systems approach to understanding human rhinovirus and influenza virus infection.

Virology. 2015 Oct 1;486:146-157

Authors: Kim TK, Bheda-Malge A, Lin Y, Sreekrishna K, Adams R, Robinson MK, Bascom CC, Tiesman JP, Isfort RJ, Gelinas R

Abstract
Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild. In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days. We modeled host responses to these viral infections with time and documented the qualitative and quantitative differences in innate immune activation and regulation.

PMID: 26437235 [PubMed – as supplied by publisher]

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Cutting Edge: AhR Is a Molecular Target of Calcitriol in Human T Cells.

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Cutting Edge: AhR Is a Molecular Target of Calcitriol in Human T Cells.

J Immunol. 2015 Aug 14;

Authors: Takami M, Fujimaki K, Nishimura MI, Iwashima M

Abstract
The immunoregulatory functions of vitamin D have been well documented in various immunological disorders, including multiple sclerosis, arthritis, and asthma. IL-10 is considered a chief effector molecule that promotes the vitamin D-induced immunosuppressive states of T cells and accessory cells. In this article, we demonstrate that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), has a profound inhibitory effect on the development of human Th9, a CD4 T cell subset that is highly associated with asthma, in an IL-10-independent manner. Our data show that calcitriol represses the expression of BATF, a transcription factor essential for Th9, via suppressing the expression of aryl hydrocarbon receptor, without an increase in IL-10. The data show a novel link between vitamin D and two key transcription factors involved in T cell differentiation.

PMID: 26276877 [PubMed – as supplied by publisher]

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Soluble Guanylate Cyclase Modulators Blunt Hyperoxia Effects on Calcium Responses of Developing Human Airway Smooth Muscle.

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Soluble Guanylate Cyclase Modulators Blunt Hyperoxia Effects on Calcium Responses of Developing Human Airway Smooth Muscle.

Am J Physiol Lung Cell Mol Physiol. 2015 Aug 7;:ajplung.00232.2015

Authors: Britt RD, Thompson MA, Kuipers I, Stewart A, Vogel ER, Thu J, Martin RJ, Pabelick CM, Prakash YS

Abstract
Exposure to moderate hyperoxia in prematurity contributes to subsequent airway dysfunction and increases the risk of developing recurrent wheeze and asthma. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic GMP (cGMP) axis modulates airway tone by regulating airway smooth muscle (ASM) intracellular Ca(2+) ([Ca(2+)]i) and contractility. However, the effects of hyperoxia on this axis in the context of Ca(2+)/contractility are not known. In developing human ASM, we explored the effects of novel drugs that activate sGC independent of NO, on alleviating hyperoxia (50% oxygen)-induced enhancement of Ca(2+) responses to bronchoconstrictor agonist. Treatment with BAY 41-2272 (sGC stimulator) and BAY 60-2770 (sGC activator) increased cGMP levels during exposure to 50% O2. Although 50% O2 did not alter sGC?1 and sGC?1 expression, BAY 60-2770 did increase sGC?1 expression. BAY 41-2272 and BAY 60-2770 blunted Ca(2+) responses to histamine in cells exposed to 50% O2. The effects of BAY 41-2272 and BAY 60-2770 were reversed by protein kinase G inhibition. These novel data demonstrate that BAY 41-2272 and BAY 60-2770 stimulate production of cGMP and blunt hyperoxia-induced increases in Ca(2+) responses in developing ASM. Accordingly, sGC stimulators/activators may be a useful therapeutic strategy in improving bronchodilation in preterm infants.

PMID: 26254425 [PubMed – as supplied by publisher]

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Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity.

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Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity.

Pediatr Neonatol. 2015 May 23;

Authors: Pancham K, Sami I, Perez GF, Huseni S, Kurdi B, Rose MC, Rodriguez-Martinez CE, Nino G

Abstract
BACKGROUND: Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same family as that of respiratory syncytial virus (RSV). Premature children are at high risk of severe RSV infections, however, it is unclear whether HMPV infection is more severe in hospitalized children with a history of severe prematurity.
METHODS: We conducted a retrospective analysis of the clinical respiratory presentation of all polymerase chain reaction-confirmed HMPV infections in preschool-age children (?5 years) with and without history of severe prematurity (<32 weeks gestation). Respiratory distress scores were developed to examine the clinical severity of HMPV infections. Demographic and clinical variables were obtained from reviewing electronic medical records.
RESULTS: A total of 571 preschool children were identified using polymerase chain reaction-confirmed viral respiratory tract infection during the study period. HMPV was identified as a causative organism in 63 cases (11%). Fifty-eight (n = 58) preschool-age children with HMPV infection were included in this study after excluding those with significant comorbidities. Our data demonstrated that 32.7% of children admitted with HMPV had a history of severe prematurity. Preschool children with a history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity, and history of asthma.
CONCLUSION: Our study suggests that HMPV infection causes significant disease burden among preschool children with a history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations.

PMID: 26117550 [PubMed – as supplied by publisher]

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