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2012-12-11

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cc-by (c) García-García, Francesc Josep et al., 2012
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/125068

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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https://doi.org/10.1371/journal.pone.0051281

Resum

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.

Matèries

Asma, Aspirina, Transducció de senyal cel·lular

Matèries (anglès)

Asthma, Aspirin, Cellular signal transduction

Citació

Col·leccions

Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

GARCÍA-GARCÍA, Francesc Josep, et al. Signal transduction pathways (MAPKS, NF-kB, and C/EBP) regulating COX-2 expression in nasal fibroblasts from asthma patients with aspirin intolerance. PLoS One. 2012. Vol. 7, num. 12, pags. e51281. ISSN 1932-6203. [consulted: 19 of August of 2026]. Available at: https://hdl.handle.net/2445/125068

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