Signal transduction pathways (MAPKs, NF-κB, and C/EBP) regulating COX-2 expression in nasal fibroblasts from asthma patients with aspirin intolerance.
PLoS One
; 7(12): e51281, 2012.
Article
en En
| MEDLINE
| ID: mdl-23240010
ABSTRACT
BACKGROUND:
Recent studies have revealed that cyclooxygenase-2 (COX-2) expression is down-regulated in aspirin-induced asthma (AIA). Various signal pathways (MAPKs, NF-κB and C/EBP) are involved in COX-2 regulation.OBJECTIVE:
To investigate the regulation of COX-2 expression through MAP-kinase pathway activation and nuclear factor translocation in aspirin-induced asthma (AIA).METHODS:
Fibroblasts were isolated from specimens of nasal mucosa (NM, Nâ=â5) and nasal polyps (NP, Nâ=â5). After IL-1ß (1 ng/ml) incubation, COX-2 and phosphorylated forms of ERK, JNK and p38 MAPK were measured by Western blot. MAPK's role in IL-1ß-induced COX-2 expression was assessed by treating cells with ERK (PD98059), JNK (SP600125) and p38 MAPK (SB203580) inhibitors (0.1-10 µM) prior to IL-1ß exposure. NF-κB and C/EBP nuclear translocation was measured by Western blot and TransAM® after IL-1ß (10 ng/ml) exposure.RESULTS:
No differences were observed in the MAPK phosphorylation time-course between NM and NP-AIA fibroblasts. The p38 MAPK inhibitor at 10 µM significantly reduced IL-1ß-induced COX-2 expression in NM fibroblasts (85%). In NP-AIA fibroblasts the COX-2 inhibition (65%) at 1 and 10 µM was not statistically significant compared to non-treated cells. ERK and JNK inhibitors had no significant effect in either the NM or NP-AIA cultures. The effect of IL-1ß on NF-κB and C/EBP subunits' nuclear translocation was similar between NM and NP-AIA fibroblasts.CONCLUSIONS:
These results suggest that p38 MAPK is the only MAPK involved in IL-1ß-induced COX-2 expression. NM and NP-AIA fibroblasts have similar MAPK phosphorylation dynamics and nuclear factor translocation (NF-κB and C/EBP). COX-2 downregulation observed in AIA patients appears not to be caused by differences in MAPK dynamics or transcription factor translocation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Ciclooxigenasa 2
/
Asma Inducida por Aspirina
Límite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2012
Tipo del documento:
Article
País de afiliación:
España