Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9899133 | International Journal of Medical Microbiology | 2005 | 8 Pages |
Abstract
Enteric Yersinia bacteria trigger transcription and secretion of the proinflammatory chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in epithelial cells. Both chemokines are controlled by NF-κB. The NF-κB-binding site in the IL-8 promoter preferentially binds Rel p65/p65 homodimers and p50/p65 heterodimers while the NF-κB-binding motifs of the MCP-1 promoter preferably bind p50/p65 heterodimers and p50/p50 homodimers. Sesquiterpene lactones inhibit the transcription factor NF-κB by alkylating the p65 subunit. In this study we investigated the inhibitory effects of sesquiterpene lactones and the NF-κB inhibitor SN50 on NF-κB p50 and p65 subunits in Yersinia-triggered IL-8 and MCP-1 production. The sesquiterpene lactones blocked Yersinia-triggered IL-8 and MCP-1 production in a dose-dependent manner. In contrast, SN50 inhibited IL-8 production at high concentrations whereas it diminished the amount of secreted MCP-1 significantly already at low concentrations. By means of electrophoretic mobility shift assays we demonstrate that sesquiterpene lactones inhibit Yersinia-triggered activation of NF-κB by inhibiting Rel p65, but not Rel p50. Our results also demonstrate that SN50 is useful for inhibition of nuclear translocation of the NF-κB p50 subunit but cannot be considered a general NF-κB inhibitor.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry, Genetics and Molecular Biology (General)
Authors
Guntram A. Grassl, Sabine Fessele, Irmgard Merfort, Maja T. Lindenmeyer, Victor Castro, Renato Murillo, Peter J. Nelson, Ingo B. Autenrieth,