Cells Archives - Page 5 of 6 - World Asthma Foundation

August 23, 2012

Restoration of Corticosteroid Sensitivity by p38 Mitogen Activated Protein Kinase Inhibition in Peripheral Blood Mononuclear Cells from Severe Asthma.

Restoration of Corticosteroid Sensitivity by p38 Mitogen Activated Protein Kinase Inhibition in Peripheral Blood Mononuclear Cells from Severe Asthma.

PLoS One. 2012;7(7):e41582

Authors: Mercado N, Hakim A, Kobayashi Y, Meah S, Usmani OS, Chung KF, Barnes PJ, Ito K

Abstract
BACKGROUND: Severe asthma accounts for a small number of asthmatics but represents a disproportionate cost to health care systems. The underlying mechanism in severe asthma remains unknown but several mechanisms are likely to be involved because of a very heterogeneous profile. We investigated the effects of a p38MAPK inhibitor in corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from severe asthmatics and the profile of its responders.
METHODOLOGY/PRINCIPAL FINDINGS: Corticosteroid sensitivity was determined by measuring dexamethasone inhibition of CD3/28 and TNF-? induced IL-8 production in PBMCs by using ELISA. PBMCs from severe asthmatics were relatively less sensitive to dexamethasone (Dex) as compared to those of non-severe asthmatics and healthy volunteers. The IC(50) values of Dex negatively correlated with decreased glucocorticoid receptor (GR) nuclear translocation assessed using immunocytochemistry (r?=?-0.65; p<0.0005) and with decreased FEV(1) (% predicted) (r?=?0.6; p<0.0005). A p38?/? inhibitor (SB203580) restored Dex-sensitivity in a subpopulation of severe asthma that was characterized by a defective GR nuclear translocation, clinically by lower FEV(1) and higher use of oral prednisolone. We also found that SB203580 partially inhibited GR phosphorylation at serine 226, resulting in increased GR nuclear translocation in IL-2/IL-4 treated corticosteroid insensitive U937s.
CONCLUSIONS/SIGNIFICANCE: p38MAPK?/? is involved in defective GR nuclear translocation due to phosphorylation at Ser226 and this will be a useful biomarker to identify responders to p38MAPK?/? inhibitor in the future.

PMID: 22911818 [PubMed – in process]

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August 8, 2012

Chlamydia muridarum Lung Infection in Infants Alters Hematopoietic Cells to Promote Allergic Airway Disease in Mice.

Chlamydia muridarum Lung Infection in Infants Alters Hematopoietic Cells to Promote Allergic Airway Disease in Mice.

PLoS One. 2012;7(8):e42588

Authors: Starkey MR, Kim RY, Beckett EL, Schilter HC, Shim D, Essilfie AT, Nguyen DH, Beagley KW, Mattes J, Mackay CR, Horvat JC, Hansbro PM

Abstract
BACKGROUND: Viral and bacterial respiratory tract infections in early-life are linked to the development of allergic airway inflammation and asthma. However, the mechanisms involved are not well understood. We have previously shown that neonatal and infant, but not adult, chlamydial lung infections in mice permanently alter inflammatory phenotype and physiology to increase the severity of allergic airway disease by increasing lung interleukin (IL)-13 expression, mucus hyper-secretion and airway hyper-responsiveness. This occurred through different mechanisms with infection at different ages. Neonatal infection suppressed inflammatory responses but enhanced systemic dendritic cell:T-cell IL-13 release and induced permanent alterations in lung structure (i.e., increased the size of alveoli). Infant infection enhanced inflammatory responses but had no effect on lung structure. Here we investigated the role of hematopoietic cells in these processes using bone marrow chimera studies.
METHODOLOGY/PRINCIPAL FINDINGS: Neonatal (<24-hours-old), infant (3-weeks-old) and adult (6-weeks-old) mice were infected with C. muridarum. Nine weeks after infection bone marrow was collected and transferred into recipient age-matched irradiated naïve mice. Allergic airway disease was induced (8 weeks after adoptive transfer) by sensitization and challenge with ovalbumin. Reconstitution of irradiated naïve mice with bone marrow from mice infected as neonates resulted in the suppression of the hallmark features of allergic airway disease including mucus hyper-secretion and airway hyper-responsiveness, which was associated with decreased IL-13 levels in the lung. In stark contrast, reconstitution with bone marrow from mice infected as infants increased the severity of allergic airway disease by increasing T helper type-2 cell cytokine release (IL-5 and IL-13), mucus hyper-secretion, airway hyper-responsiveness and IL-13 levels in the lung. Reconstitution with bone marrow from infected adult mice had no effects.
CONCLUSIONS: These results suggest that an infant chlamydial lung infection results in long lasting alterations in hematopoietic cells that increases the severity of allergic airway disease in later-life.

PMID: 22870337 [PubMed – in process]

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July 8, 2012

Reprogramming Asthma-promoting Cells Could Help Treat Asthma – IBTimes.co.uk

IBTimes.co.uk

Reprogramming Asthma-promoting Cells Could Help Treat Asthma
IBTimes.co.uk
Scientists find a new treatment for asthma by reprogramming some asthma-promoting immune cells.

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May 8, 2012

University of Michigan researchers identify cells resistant to asthma treatments – AnnArbor.com

CBS Local

University of Michigan researchers identify cells resistant to asthma treatments
AnnArbor.com
Researchers at the University of Michigan Health System have discovered the type of cell that appears to cause asthma symptoms even when treated by medicine from an inhaler. The findings may help scientists develop new treatment options, …
Scientists discover new type of cell with a key role in treatment-resistant asthmaMarketWatch (press release)

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May 2, 2012

Asthma Prevention by Lactobacillus Rhamnosus in a Mouse Model is Associated With CD4(+)CD25(+)Foxp3(+) T Cells.

Asthma Prevention by Lactobacillus Rhamnosus in a Mouse Model is Associated With CD4(+)CD25(+)Foxp3(+) T Cells.

Allergy Asthma Immunol Res. 2012 May;4(3):150-6

Authors: Jang SO, Kim HJ, Kim YJ, Kang MJ, Kwon JW, Seo JH, Kim HY, Kim BJ, Yu J, Hong SJ

Abstract
PURPOSE: Probiotic bacteria can induce immune regulation or immune tolerance in allergic diseases. The underlying mechanisms have been recently investigated, but are still unclear. The aim of this study was to evaluate the protective effects of the probiotic Lactobacillus rhamnosus (Lcr35) in a mouse model of asthma and to identify its mechanism of action.
METHODS: Lcr35 was administered daily by the oral route at a dosage of 1×10(9) CFU/mouse in BALB/c mice for 7 days before the first sensitization. Clinical parameters and regulatory T (Treg) cells were examined. The role of CD4(+)CD25(+)Foxp3(+) Treg cells was analyzed using a Treg cell-depleting anti-CD25 monoclonal antibody (mAb).
RESULTS: Airway hyperresponsiveness, total IgE production, pulmonary eosinophilic inflammation, and splenic lymphocyte proliferation were suppressed after Lcr35 treatment. Th1 (IFN-?) and Th2 (IL-4, IL-5, and IL-13) cytokines in the serum were suppressed, and the percentage of CD4(+)CD25(+)Foxp3(+) Treg cells in the spleen was significantly increased in the Lcr35 treatment group. Anti-CD25 mAb administration abolished the protective effects of Lcr35, indicating that CD4(+) CD25(+)Foxp3(+) Treg cells are essential in mediating the activity of Lcr35.
CONCLUSIONS: Oral administration of Lcr35 attenuated the features of allergic asthma in a mouse model and induced immune regulation by a CD4(+)CD25(+)Foxp3(+) Treg cell-mediated mechanism.

PMID: 22548208 [PubMed – in process]

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February 18, 2012

1?,25-Dihydroxyvitamin D3 promotes CD200 expression by human peripheral and airway-resident T cells.

1?,25-Dihydroxyvitamin D3 promotes CD200 expression by human peripheral and airway-resident T cells.

Thorax. 2012 Feb 14;

Authors: Dimeloe S, Richards DF, Urry ZL, Gupta A, Stratigou V, Farooque S, Saglani S, Bush A, Hawrylowicz CM

Abstract
BackgroundCD200, a cell-surface immunoglobulin-like molecule expressed by immune and stromal cells, dampens the pro-inflammatory activity of tissue-resident innate cells via its receptor, CD200R. This interaction appears critical for peripheral immune tolerance, particularly in the airways where excessive inflammation is undesirable. Vitamin D contributes to pulmonary health and promotes regulatory immune pathways, therefore its influence on CD200 and CD200R was investigated.MethodsCD200 and CD200R expression were assessed by qPCR and immunoreactivity of human lymphoid, myeloid and epithelial cells following 1?,25-dihydroxyvitamin D3 (1?,25VitD3) exposure in vitro and in peripheral T cells following 1?,25VitD3 oral ingestion in vivo. The effect of 1?25VitD3 was also assessed in human airway-resident cells.Results1?25VitD3 potently upregulated CD200 on peripheral human CD4+ T cells in vitro, and in vivo there was a trend towards upregulation in healthy, but not asthmatic individuals. CD200R expression was not modulated in any cells studied. CD200 induction was observed to a lesser extent in CD8+ T cells and not in B cells or airway epithelium. T cells isolated from the human airway also responded strongly to 1?25VitD3 to upregulate CD200.ConclusionsThe capacity of 1?,25-dihydroxyvitamin D3 to induce CD200 expression by peripheral and respiratory tract T cells identifies an additional pathway via which vitamin D can restrain inflammation in the airways to maintain respiratory health.

PMID: 22334534 [PubMed – as supplied by publisher]

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January 29, 2012

Chlamydophila pneumonia inhibits the corticosteroid-induced suppressions of metalloproteinase-9 and tissue inhibitor metalloproteinase-1 secretion by human peripheral blood mononuclear cells.

Chlamydophila pneumonia inhibits the corticosteroid-induced suppressions of metalloproteinase-9 and tissue inhibitor metalloproteinase-1 secretion by human peripheral blood mononuclear cells.

J Med Microbiol. 2012 Jan 26;

Authors: Park CS, Lee YS, Kwon HS, Lee TH, Kim TB, Moon KA, Yoo B, Moon HB, Cho YS

Abstract
Chlamydophila pneumoniae infection has been suggested to be associated with severe asthma characterized by persistent airway limitation, which may be related to airway remodeling. We investigated whether C. pneumoniae infection affected the secretion of metalloproteinase-9 (MMP9) and tissue inhibitor metalloproteinase-1 (TIMP1), and altered the responsiveness of inflammatory cells to corticosteroids. Human peripheral blood mononuclear cells (PBMC) were cultured in vitro in the presence or absence of C. pneumoniae. Secretion of both MMP9 and TIMP1 was strongly suppressed by dexamethasone treatment in uninfected cells. MMP9 secretion was also significantly inhibited by dexamethasone in C. pneumoniae-infected cells, but TIMP1 secretion was not; hence the MMP9 to TIMP1 ratio decreased. Interestingly, expression of human glucocorticoid receptor (GR)?, which is believed to confer resistance to corticosteroids, was enhanced by dexamethasone treatment in C. pneumoniae-infected PBMC. We conclude that C. pneumoniae infection may promote airway remodeling by decreasing the ratio of MMP9 to TIMP1 secreted by inflammatory cells, and by altering cellular responsiveness to corticosteroids.

PMID: 22282461 [PubMed – as supplied by publisher]

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December 18, 2011

[Lipid composition of cells and low-density lipoproteins in blood serum of humans and some vertebrates species].

[Lipid composition of cells and low-density lipoproteins in blood serum of humans and some vertebrates species].

Zh Evol Biokhim Fiziol. 2011 Sep-Oct;47(5):365-74

Authors:

Abstract
To investigate interaction of atherogenic low-density lipoproteins (LDL) with erythrocytic membrane, the content of lipid components in blood cells and serum LDL was studied in human in norm (donors) and in 12 species of vertebrates (the mammals non-predisposed to atherosclerosis – birds and fish). Lipid composition of blood cells and LDL was analyzed also in patients with pathologies: ischemic heart disease (IHD), bronchial asthma (BA), and chronic obstructive bronchitis (COB), and in 2 species of mammals predisposed to atherosclerosis, in whose blood LDL predominates. The content of lipids in cells and LDL of the studied vertebrates has been found to depend on their taxonomy and the clear trends both to an increase of the cholesterol content and to a decrease if the phosphatidylcholine level in patients, particu- larly with IHD, and on a rise of the ratio of the content of the more saturated sphingomyelin and cholesterol to the less saturated phosphatidylcholine from the lower to the higher organisms, including humans (donors). The highest levels of free cholesterol in blood cells, of total cholesterol in LDL, and of ration of the cholesterol/phosphatidylcholine content have been revealed in patients, especially with 1HB, and in the mammals predisposed to atherosclerosis, i. e., in representatives with predominance of blood LDL, unlike donors and the mammals resistant to atherosclerosis. The highest parameters of lipid components were determined in cells and LDL inhuman with IHD. The lipid LDL composition affects directly the composition and ratio of lipids in blood cells.

PMID: 22145317 [PubMed – in process]

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December 14, 2011

Work in cells, animals, patients reveals toxin’s role in asthma – PhysOrg.com (press release)

PhysOrg.com (press release)

Work in cells, animals, patients reveals toxin's role in asthma
PhysOrg.com (press release)
Dr. Baseman leads studies of whether a common respiratory bacterial pathogen and the toxin it makes are initiating and intensifying asthma and other allergic diseases. Credit: UT Health Science Center San Antonio Five years ago, microbiologists at The …

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December 2, 2011