Dauletbaev N, Lam J, Eklove D, Iskandar M, Lands LC
Ibuprofen Modulates NF-kappaB Activity but Not IL-8 Production in Cystic Fibrosis Respiratory Epithelial Cells. [JOURNAL ARTICLE]
Respiration 2009 Nov 3.
Background: High-dose ibuprofen is clinically effective in cystic fibrosis (CF); however, its molecular mechanisms are poorly understood.
Objective: To test the hypothesis that clinically relevant concentrations of ibuprofen suppress activation of nuclear factor (NF)-kappaB and thus down-regulate stimulated interleukin (IL)-8 production in CF respiratory epithelial cells.
Methods: The majority of experiments were conducted in CFTE29o- cells (F508del-mutated CF transmembrane regulator, CFTR). Key experiments were confirmed in CFBE41o- cells (F508del-mutated CFTR) and 1HAEo- cells (wild-type CFTR). NF-kappaB and IL-8 were stimulated with tumour necrosis factor (TNF)-alpha or IL-1beta. NF-kappaB and IL-8 suppression by ibuprofen (480 muM) was compared to dexamethasone (5 nM).
Results: Both TNF-alpha and IL-1beta activated NF-kappaB and stimulated IL-8 production. Both ibuprofen and dexamethasone demonstrated comparably modest suppression of NF-kappaB transcriptional activity. However, ibuprofen had no effect on stimulated IL-8 mRNA and protein. By contrast, dexamethasone significantly down-regulated stimulated IL-8 mRNA and protein.
Conclusions: The present data do not support the hypothesis that ibuprofen down-regulates IL-8 production in response to TNF-alpha and IL-1beta in CF respiratory epithelium. Suppression of NF-kappaB transcriptional activity does not discriminate between anti-inflammatory drugs with or without effects on IL-8 production. We speculate that NF-kappaB-independent mechanisms may be responsible for anti-IL-8 effects of dexamethasone.
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