PMID- 16325549
OWN - NLM
STAT- MEDLINE
DCOM- 20060216
LR  - 20061115
IS  - 1438-4221 (Print)
IS  - 1438-4221 (Linking)
VI  - 295
IP  - 8
DP  - 2005 Dec
TI  - Sesquiterpene lactones inhibit Yersinia invasin protein-induced IL-8 and MCP-1 
      production in epithelial cells.
PG  - 531-8
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.
FAU - Grassl, Guntram A
AU  - Grassl GA
AD  - Institut fur Medizinische Mikrobiologie und Krankenhaushygiene, 
      Universitatsklinikum Tubingen, Elfriede-Aulhorn-Str. 6, D-72060 Tubingen, 
      Germany.
FAU - Fessele, Sabine
AU  - Fessele S
FAU - Merfort, Irmgard
AU  - Merfort I
FAU - Lindenmeyer, Maja T
AU  - Lindenmeyer MT
FAU - Castro, Victor
AU  - Castro V
FAU - Murillo, Renato
AU  - Murillo R
FAU - Nelson, Peter J
AU  - Nelson PJ
FAU - Autenrieth, Ingo B
AU  - Autenrieth IB
LA  - eng
PT  - Journal Article
DEP - 20050913
PL  - Germany
TA  - Int J Med Microbiol
JT  - International journal of medical microbiology : IJMM
JID - 100898849
RN  - 0 (Adhesins, Bacterial)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Peptides)
RN  - 0 (RNA, Messenger)
RN  - 0 (SN50 peptide)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Transcription Factor RelA)
RN  - 114073-91-5 (invasin, Yersinia)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adhesins, Bacterial/*immunology
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - DNA/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelial Cells/drug effects/*microbiology
MH  - HeLa Cells
MH  - Humans
MH  - Interleukin-8/*biosynthesis/genetics
MH  - NF-kappa B/antagonists & inhibitors
MH  - NF-kappa B p50 Subunit/antagonists & inhibitors/metabolism
MH  - Peptides/pharmacology
MH  - Protein Binding
MH  - RNA, Messenger/analysis
MH  - Sesquiterpenes/*pharmacology
MH  - Transcription Factor RelA/antagonists & inhibitors/metabolism
MH  - Yersinia enterocolitica/*immunology
EDAT- 2005/12/06 09:00
MHDA- 2006/02/17 09:00
CRDT- 2005/12/06 09:00
PHST- 2005/06/16 00:00 [received]
PHST- 2005/07/04 00:00 [accepted]
PHST- 2005/12/06 09:00 [pubmed]
PHST- 2006/02/17 09:00 [medline]
PHST- 2005/12/06 09:00 [entrez]
AID - S1438-4221(05)00114-1 [pii]
AID - 10.1016/j.ijmm.2005.07.012 [doi]
PST - ppublish
SO  - Int J Med Microbiol. 2005 Dec;295(8):531-8. doi: 10.1016/j.ijmm.2005.07.012. Epub 
      2005 Sep 13.