Appendix - CNIC

SCIENTIFIC REPORT ´09
> RESEARCH INTEREST
Our group is interested in the molecular basis of the
inflammatory response and in the search of new therapeutic
agents with anti-inflammatory properties. Many natural
products are used for the prevention and treatment of
inflammatory conditions. The largest and most widespread
class of these compounds is the terpenoids (also referred to as
terpenes). As part of a program of research into the biological
activities of terpenoids, we are evaluating the antiatherogenic
and antiinflammatory potential of several natural product
derivatives. To investigate the mechanism of action of this
class of compounds, we are studying targets relevant to the
regulation of the inflammatory response. We have recently
shown that several labdane derivatives inhibit inflammatory
processes in vitro and in vivo through a mechanism involving
inhibition of NF-KB activity. This effect seems to be related to
the ability of these compounds to reduce IKBα degradation
and phosphorylation, leading to inhibition of NF-KB
translocation. These findings establish the potential of
labdane diterpenoids as alternatives to current treatments for
the treatment of inflammatory diseases.
We are also investigating the role of the tumor suppressor ARF
in immune responses. We recently identified a decreased
inflammatory response in ARF-deficient animals associated
with impaired activation of toll-like receptors, particularly
TLR4. We are currently investigating the impact of ARF
deficiency and TLR signaling in models of cardiovascular
disease.
> MAJOR GRANTS
- Ministerio de Ciencia e Innovación. FIS (P1080070)
SELECTED PUBLICATIONS
de las Heras B, Hortelano S. Molecular basis of the anti-inflammatory effects of terpenoids. Inflamm Allergy Drug Targets (2009) 8:
28-39
Giron N, Traves PG, Rodriguez B, Lopez-Fontal R, Bosca L, Hortelano S*, de las Heras B. Supression of inflammatory responses by
labdane-type diterpenoids. Toxicol Appl Pharmacol (2008) 228: 179-89
* Corresponding author
Diaz-Viciedo R, Hortelano S, Giron N, Masso JM, Rodriguez B, Villar A, de las Heras B. Modulation of inflammatory responses by
diterpene acids from Helianthus annuus L. Biochem Biophys Res Commun. (2008) 369: 761-6
28
2 Regenerative Cardiology
Toll-like receptors and innate immunity
in cardiovascular disease and generation
Head of Laboratory: Sonsoles Hortelano
Scientific Collaborator: Alfonso Luque
Predoctoral Researcher: Raquel López Fontal
Technician: Gabriel Bergazyn Liberman
Main signaling pathways inhibited by diterpenoids.