Sesquiterpene lactones as inhibitors of IL-8 expression in HeLa cells
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Sesquiterpene lactones as inhibitors of IL-8 expression in HeLa cells. / Lindenmeyer, Maja T; Hrenn, Andrea; Kern, Claudia; Castro, Victor; Murillo, Renato; Müller, Stefan; Laufer, Stefan; Schulte-Mönting, Jürgen; Siedle, Bettina; Merfort, Irmgard.
In: BIOORGAN MED CHEM, Vol. 14, No. 8, 15.04.2006, p. 2487-97.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Sesquiterpene lactones as inhibitors of IL-8 expression in HeLa cells
AU - Lindenmeyer, Maja T
AU - Hrenn, Andrea
AU - Kern, Claudia
AU - Castro, Victor
AU - Murillo, Renato
AU - Müller, Stefan
AU - Laufer, Stefan
AU - Schulte-Mönting, Jürgen
AU - Siedle, Bettina
AU - Merfort, Irmgard
PY - 2006/4/15
Y1 - 2006/4/15
N2 - Twenty-four structurally different SLs were studied for their inhibition on IL-8 production in HeLa229 cells and different IC50-values were obtained. QSAR analyses revealed that the alpha-methylene-gamma-lactone and the presence and reactivity of a second reaction center, expressed by LUMO2, are the most important descriptors for IL-8. Using two SLs as examples, we demonstrated that SLs prevent DNA binding of AP-1, which has binding sites in the IL-8 promoter together with NF-kappaB and C/EBP, and that this is probably due to directly targeting AP-1. p38 MAPK, which plays a role in AP-1 activation as well as in IL-8 regulation, was not influenced by SLs. These data show that NF-kappaB and AP-1, and consequently IL-8 may be interesting targets in antiinflammation research and that the small molecules of SLs may be powerful candidates with promising properties for therapeutic modulation of the inflammatory response.
AB - Twenty-four structurally different SLs were studied for their inhibition on IL-8 production in HeLa229 cells and different IC50-values were obtained. QSAR analyses revealed that the alpha-methylene-gamma-lactone and the presence and reactivity of a second reaction center, expressed by LUMO2, are the most important descriptors for IL-8. Using two SLs as examples, we demonstrated that SLs prevent DNA binding of AP-1, which has binding sites in the IL-8 promoter together with NF-kappaB and C/EBP, and that this is probably due to directly targeting AP-1. p38 MAPK, which plays a role in AP-1 activation as well as in IL-8 regulation, was not influenced by SLs. These data show that NF-kappaB and AP-1, and consequently IL-8 may be interesting targets in antiinflammation research and that the small molecules of SLs may be powerful candidates with promising properties for therapeutic modulation of the inflammatory response.
KW - Base Sequence
KW - CCAAT-Enhancer-Binding Proteins
KW - DNA Primers
KW - Down-Regulation
KW - Electrophoretic Mobility Shift Assay
KW - Enzyme-Linked Immunosorbent Assay
KW - HeLa Cells
KW - Humans
KW - Interleukin-8
KW - Jurkat Cells
KW - Lactones
KW - NF-kappa B
KW - Promoter Regions, Genetic
KW - RNA, Messenger
KW - Sesquiterpenes
KW - Structure-Activity Relationship
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.bmc.2005.11.027
DO - 10.1016/j.bmc.2005.11.027
M3 - SCORING: Journal article
C2 - 16326104
VL - 14
SP - 2487
EP - 2497
JO - BIOORGAN MED CHEM
JF - BIOORGAN MED CHEM
SN - 0968-0896
IS - 8
ER -