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Título:
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Signal transduction pathways (MAPKS, NF-kB, and C/EBP) regulating COX-2 expression in nasal fibroblasts from asthma patients with aspirin intolerance
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Autor/a:
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García-García, Francesc Josep; Mullol i Miret, Joaquim; Pérez-González, Maria; Pujols Tarrés, Laura; Alobid, Isam; Roca i Ferrer, Jordi; Picado Vallés, César
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Notas:
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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, N = 5) and nasal polyps (NP, N = 5). After IL-1β (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-1β-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-1β exposure. NF-κB and C/EBP nuclear translocation was measured by Western blot and TransAM® after IL-1β (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-1β-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-1β 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-1β-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. |
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Materia(s):
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-Asma
-Aspirina
-Transducció de senyal cel·lular
-Asthma
-Aspirin
-Cellular signal transduction |
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Derechos:
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cc-by (c) García-García, Francesc Josep et al., 2012
http://creativecommons.org/licenses/by/3.0/es
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Tipo de documento:
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Artículo
Artículo - Versión publicada |
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Editor:
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Public Library of Science (PLoS)
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Compartir:
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