Sesquiterpene lactones inhibit Yersinia invasin protein-induced IL-8 and MCP-1 production in epithelial cells
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Sesquiterpene lactones inhibit Yersinia invasin protein-induced IL-8 and MCP-1 production in epithelial cells. / Grassl, Guntram A; Fessele, Sabine; Merfort, Irmgard; Lindenmeyer, Maja T; Castro, Victor; Murillo, Renato; Nelson, Peter J; Autenrieth, Ingo B.
in: INT J MED MICROBIOL, Jahrgang 295, Nr. 8, 12.2005, S. 531-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Sesquiterpene lactones inhibit Yersinia invasin protein-induced IL-8 and MCP-1 production in epithelial cells
AU - Grassl, Guntram A
AU - Fessele, Sabine
AU - Merfort, Irmgard
AU - Lindenmeyer, Maja T
AU - Castro, Victor
AU - Murillo, Renato
AU - Nelson, Peter J
AU - Autenrieth, Ingo B
PY - 2005/12
Y1 - 2005/12
N2 - 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-kappaB. The NF-kappaB-binding site in the IL-8 promoter preferentially binds Rel p65/p65 homodimers and p50/p65 heterodimers while the NF-kappaB-binding motifs of the MCP-1 promoter preferably bind p50/p65 heterodimers and p50/p50 homodimers. Sesquiterpene lactones inhibit the transcription factor NF-kappaB by alkylating the p65 subunit. In this study we investigated the inhibitory effects of sesquiterpene lactones and the NF-kappaB inhibitor SN50 on NF-kappaB 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-kappaB by inhibiting Rel p65, but not Rel p50. Our results also demonstrate that SN50 is useful for inhibition of nuclear translocation of the NF-kappaB p50 subunit but cannot be considered a general NF-kappaB inhibitor.
AB - 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-kappaB. The NF-kappaB-binding site in the IL-8 promoter preferentially binds Rel p65/p65 homodimers and p50/p65 heterodimers while the NF-kappaB-binding motifs of the MCP-1 promoter preferably bind p50/p65 heterodimers and p50/p50 homodimers. Sesquiterpene lactones inhibit the transcription factor NF-kappaB by alkylating the p65 subunit. In this study we investigated the inhibitory effects of sesquiterpene lactones and the NF-kappaB inhibitor SN50 on NF-kappaB 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-kappaB by inhibiting Rel p65, but not Rel p50. Our results also demonstrate that SN50 is useful for inhibition of nuclear translocation of the NF-kappaB p50 subunit but cannot be considered a general NF-kappaB inhibitor.
KW - Adhesins, Bacterial
KW - Chemokine CCL2
KW - DNA
KW - Electrophoretic Mobility Shift Assay
KW - Enzyme-Linked Immunosorbent Assay
KW - Epithelial Cells
KW - HeLa Cells
KW - Humans
KW - Interleukin-8
KW - NF-kappa B
KW - NF-kappa B p50 Subunit
KW - Peptides
KW - Protein Binding
KW - RNA, Messenger
KW - Sesquiterpenes
KW - Transcription Factor RelA
KW - Yersinia enterocolitica
KW - Journal Article
U2 - 10.1016/j.ijmm.2005.07.012
DO - 10.1016/j.ijmm.2005.07.012
M3 - SCORING: Journal article
C2 - 16325549
VL - 295
SP - 531
EP - 538
JO - INT J MED MICROBIOL
JF - INT J MED MICROBIOL
SN - 1438-4221
IS - 8
ER -