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 microM) 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. Copyright 2009 S. Karger AG, Basel.
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 microM) 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. Copyright 2009 S. Karger AG, Basel.
Authors: Munir M Zaman; Camilia R Martin; Charlotte Andersson; Abdul Q Bhutta; Joanne E Cluette-Brown; Michael Laposata; Steven D Freedman Journal: Am J Physiol Lung Cell Mol Physiol Date: 2010-07-23 Impact factor: 5.464
Authors: Parth N Shah; Kimberly R Marshall-Batty; Justin A Smolen; Jasur A Tagaev; Qingquan Chen; Christopher A Rodesney; Henry H Le; Vernita D Gordon; David E Greenberg; Carolyn L Cannon Journal: Antimicrob Agents Chemother Date: 2018-02-23 Impact factor: 5.191
Authors: Nurlan Dauletbaev; Mithun Das; Maria Cammisano; He Chen; Sareen Singh; Cora Kooi; Richard Leigh; Trevor Beaudoin; Simon Rousseau; Larry C Lands Journal: PLoS One Date: 2015-11-23 Impact factor: 3.240