title: Signal transduction pathways (MAPKs, NF-κB, and C/EBP) regulating COX-2 expression in nasal fibroblasts from asthma patients with aspirin intolerance.
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, 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.
authors.affiliation: Immunoal·lèrgia Respiratòria Clínica i Experimental (IRCE), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors.forename: Francesc Josep
authors.initials: FJ
authors.lastname: Garcia-Garcia
authors.forename: Joaquim
authors.initials: J
authors.lastname: Mullol
authors.forename: Maria
authors.initials: M
authors.lastname: Perez-Gonzalez
authors.forename: Laura
authors.initials: L
authors.lastname: Pujols
authors.forename: Isam
authors.initials: I
authors.lastname: Alobid
authors.forename: Jordi
authors.initials: J
authors.lastname: Roca-Ferrer
authors.forename: Cesar
authors.initials: C
authors.lastname: Picado
mesh_terms: D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D055963:Asthma, Aspirin-Induced / Q000378:metabolism / Q000503:physiopathology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D016328:NF-kappa B; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D001241:Aspirin