Breathe Well Live Well
Condition: Peripheral Arterial Diseases
Intervention: Drug: Active comparator (cilostazol) and Placebo comparator
Sponsors: National Cheng-Kung University Hospital; National Cheng-Kung University Hospital; Department of Health, Executive Yuan, R.O.C. (Taiwan)
Active, not recruiting – verified September 2013
View full post on ClinicalTrials.gov: asthma | received in the last 14 days
CD44 variant isoforms are specifically expressed on peripheral blood lymphocytes from asthmatic patients.
Exp Ther Med. 2012 Jul;4(1):79-83
Authors: Yang C, Liang H, Zhao H, Jiang X
Abstract
Asthma is a disease characterized by chronic airway inflammation, and Th2 cells play a critical role in initiating and sustaining asthmatic inflammation. It has been shown that CD44 expressed on CD4(+) T cells plays a critical role in the accumulation of antigen-specific Th2 cells in the development of airway hyperresponsiveness induced by antigen challenge in the airways. The aim of this study was to determine whether there are specific CD44 variant isoforms (CD44v) expressed on lymphocytes from asthmatic patients. We collected whole blood samples from 103 normal subjects, 165 subjects with asthma and 104 with pneumonia. Peripheral blood lymphocyte isolation was performed, and total RNA was extracted from the isolated lymphocytes, using nested PCR for specific CD44v amplification on lymphocytes. Demographic variables were analyzed using linear regression in order to determine whether the expression of CD44v was correlated with these demographic features. The nested PCR results revealed that CD44v5 was expressed by 55.2% of asthma patients, which was significantly higher than levels of expression in the other groups. Lower percentages of individuals in the normal subject group exhibited expression of CD44v5 and CD44v6. The data demonstrated that the percentage of individuals in the pneumonia group expressing CD44v5 was 29.0%, but a higher percentage of these patients expressed CD44v6. CD44v5 expression was positively correlated with IgE levels (p=0.032) in the asthmatic patient group, and CD44v6 was significantly positively correlated with the neutrophil count (p<0.05). CD44v5 was expressed by a higher proportion of asthmatic patients than other subjects and thus may play an important role in the pathogenesis of asthma. These findings may offer a new target for the diagnosis and treatment of asthma and may also provide insights into the mechanisms of asthma development.
PMID: 23060926 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
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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]
View full post on pubmed: asthma
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]
View full post on pubmed: asthma
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]
View full post on pubmed: asthma