Signal Transduction Pathways (MAPKs, NF-?B, and C/EBP) Regulating COX-2 Expression in Nasal Fibroblasts from Asthma Patients with Aspirin Intolerance.
PLoS One. 2012;7(12):e51281
Authors: Garcia-Garcia FJ, Mullol J, Perez-Gonzalez M, Pujols L, Alobid I, Roca-Ferrer J, Picado C
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-?B 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-1? (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-1?-induced COX-2 expression was assessed by treating cells with ERK (PD98059), JNK (SP600125) and p38 MAPK (SB203580) inhibitors (0.1-10 �M) prior to IL-1? exposure. NF-?B and C/EBP nuclear translocation was measured by Western blot and TransAM� after IL-1? (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 �M significantly reduced IL-1?-induced COX-2 expression in NM fibroblasts (85%). In NP-AIA fibroblasts the COX-2 inhibition (65%) at 1 and 10 �M 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-1? on NF-?B 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-1?-induced COX-2 expression. NM and NP-AIA fibroblasts have similar MAPK phosphorylation dynamics and nuclear factor translocation (NF-?B and C/EBP). COX-2 downregulation observed in AIA patients appears not to be caused by differences in MAPK dynamics or transcription factor translocation.
PMID: 23240010 [PubMed - in process]
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