Variable p-CREB expression depicts different asthma phenotypes.
Allergy
; 62(7): 787-94, 2007 Jul.
Article
en En
| MEDLINE
| ID: mdl-17573727
ABSTRACT
BACKGROUND:
Chromatin modification may play a role in inflammatory gene regulation in asthma. Cyclic adenosine mono-phosphate response element-binding protein (CREB), with the specific co-activator, the CREB-binding protein (CBP), contributes to the acetylation of chromatin and to the transcription of pro-inflammatory genes.OBJECTIVES:
To evaluate the expression of CBP and of phospho-CREB (p-CREB) in bronchial biopsies and in peripheral blood mononuclear cells (PBMC) of controls (C), untreated (UA), inhaled steroid treated (ICS) and steroid-dependent asthmatic (SDA) patients.METHODS:
We used immunohistochemistry in bronchial biopsies and western blot analysis and immunocytochemistry in PBMC.RESULTS:
Cyclic adenosine mono-phosphate response element-binding protein expression, in the epithelium was similar in all groups, while p-CREB expression was increased in UA and in SDA in comparison with ICS and C subjects (C vs UA P = 0.002, C vs SDA P = 0.007), (ICS vs SDA P = 0.005), (ICS vs UA P = 0.001). Interestingly, also in the submucosa, p-CREB was increased in UA and SDA in comparison with ICS and C subjects (C vs UA P = 0.0004) (C vs SDA P < 0.0001) (ICS vs UA P = 0.002) (ICS vs SDA P < 0.0001) and positively correlated with leukocyte infiltration within the bronchi (CD45RB+ cells). Similar results were obtained with PBMC isolated from the same patient groups. Incubation of PBMC in vitro, with fluticasone propionate, decreased the p-CREB expression induced by cytokine activation (interferon-gamma, tumor necrosis factor-alpha).CONCLUSIONS:
This study demonstrates that the expression of p-CREB is related, in asthma, to the persistent inflammation according to the disease severity. p-CREB expression can be modulated by glucocorticoids in responsive patients.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Asma
/
Índice de Severidad de la Enfermedad
/
Proteína de Unión a Elemento de Respuesta al AMP Cíclico
/
Inflamación
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Allergy
Año:
2007
Tipo del documento:
Article
País de afiliación:
Italia