NF-κΒ inhibition is ineffective in blocking cytokine-induced IL-8 production but P38 and STAT1 inhibitors are effective
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In vitro but not in vivo evidence indicates that blockade of NF-κB is effective in reducing inflammation and production of IL-8. We hypothesized that the failure of in vitro experiments to predict in vivo outcome was due to the use of short time periods of observation and the use of single cytokines to stimulate NF-κB.
HEK cells with a NF-κB reporter gene or CaCo-2 cells were stimulated with CM (IL-1-β; TNF-α, and IFN-γ) or individual cytokines in the presence and absence of NF-κB inhibitors, a STAT1 inhibitor, and/or a p38 MAPK inhibitor for periods up to 24 h. NF-κB activation, IL-8 production, and nitric oxide production were measured.
CM-induced IL-8 production in HEK cells was additive to synergistic. CM enhanced production of IL-8 at 24 h but not 4 h was independent of NF-κB. The p38 inhibitor SB203580 and the STAT1 inhibitor EGCG blocked CM-induced IL-8 production at both early and late time periods. The NF-κB inhibitors PDTC and BAY11-7082 were found to increase CM-stimulated IL-8 production in Caco-2 cells at 24 h.
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- NF-κΒ inhibition is ineffective in blocking cytokine-induced IL-8 production but P38 and STAT1 inhibitors are effective
Volume 61, Issue 9 , pp 977-985
- Cover Date
- Print ISSN
- Online ISSN
- SP Birkhäuser Verlag Basel
- Additional Links
- p38 MAPK
- Caco-2 cells
- HEK blue cells
- Industry Sectors
- Author Affiliations
- 1. Department of Research, Shriners Hospital for Children, 3229 Burnet Ave., Cincinnati, OH, 45229-3095, USA
- 2. Department of Surgery, University of Cincinnati, Cincinnati, OH, 45229, USA