Breathe Well Live Well
Conditions: Asthma; Bronchial Hyperresponsiveness
Intervention: Drug: histamine-benzylic alcohol (magistral preparation)
Sponsors: Centre Hospitalier Universitaire Saint Pierre; Centre Hospitalier Universitaire Saint Pierre
Recruiting – verified September 2013
View full post on ClinicalTrials.gov: asthma | received in the last 14 days
| Related Articles |
Programmed cell death ligand 2 regulates T(H)9 differentiation and induction of chronic airway hyperreactivity.
J Allergy Clin Immunol. 2012 Nov 19;
Authors: Kerzerho J, Maazi H, Speak AO, Szely N, Lombardi V, Khoo B, Geryak S, Lam J, Soroosh P, Van Snick J, Akbari O
Abstract
BACKGROUND: Asthma is defined as a chronic inflammatory disease of the airways; however, the underlying physiologic and immunologic processes are not fully understood. OBJECTIVE: The aim of this study was to determine whether T(H)9 cells develop in vivo in a model of chronic airway hyperreactivity (AHR) and what factors control this development. METHOD: We have developed a novel chronic allergen exposure model using the clinically relevant antigen Aspergillus fumigatus to determine the time kinetics of T(H)9 development in vivo. RESULTS: T(H)9 cells were detectable in the lungs after chronic allergen exposure. The number of T(H)9 cells directly correlated with the severity of AHR, and anti-IL-9 treatment decreased airway inflammation. Moreover, we have identified programmed cell death ligand (PD-L) 2 as a negative regulator of T(H)9 cell differentiation. Lack of PD-L2 was associated with significantly increased TGF-? and IL-1? levels in the lungs, enhanced pulmonary T(H)9 differentiation, and higher morbidity in the sensitized mice. CONCLUSION: Our findings suggest that PD-L2 plays a pivotal role in the regulation of T(H)9 cell development in chronic AHR, providing novel strategies for modulating adaptive immunity during chronic allergic responses.
PMID: 23174661 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
Sphingosine-1-phosphate induced airway hyperreactivity in rodents is mediated by the S1P3 receptor.
J Pharmacol Exp Ther. 2012 May 8;
Authors: Trifilieff A, Fozard JR
Abstract
There is a need to better understand the mechanism of airway hyperreactivity, a key feature of asthma. Evidence suggests that sphingosine-1-phosphate (S1P) could be a major player in this phenomenon. The purpose of this work was to define the S1P receptor responsible for this phenomenon. We have studied, in the rat, the effect of two S1P synthetic receptor ligands, FTY720 (which in its phosphorylated form is a potent agonist at each S1P receptor except S1P2) and AUY954 (a highly selective S1P1 agonist) on lung function in vivo. This was complemented by in vitro studies using isolated trachea from the rat, the S1P3 receptor-deficient mouse and its wild type counterpart. Following oral administration, FTY720 induced a generalized airway hyperreactivity to a range of contractile stimuli. This was observed as early as one hour post dosing, lasted for at least 24 hours and was not subject to desensitization. In both the rat and wild type mouse isolated trachea, pre-incubation with the active phosphorylated metabolite of FTY720, induced hyperresponsiveness to 5-HT. This effect was not seen in the isolated tracheas from S1P3 receptor-deficient mice. AUY954, did not mimic the effect of FTY720 either in vivo or in vitro. Our data are consistent with activation of the S1P pathway inducing a generalized airway hyperreactivity in rats and mice that is mediated by the S1P3 receptor. S1P3 receptor antagonists might prove useful as new therapeutic strategies aimed at blocking the airway hyperreactivity observed in asthma.
PMID: 22570366 [PubMed – as supplied by publisher]
View full post on pubmed: asthma