Krisztina Truta-Feles, PhD
Personal Data:
Country of Origin: Romania
PhD period: March 2006 - July 2010
Title:
Function of phosphatidylinositol-3-kinase-γamma and
SH2-containing inositol-5-phosphatase-1 in innate immunity
Project Leader: Prof. Dr. Johannes Norgauer
Abstract:
Innate immunity refers to the activation of different antigen-nonspecific
mechanisms, including immune components as well as the non-immune
defense machinery. In this context, those cellular components of
the innate immune system are designed to recognize a few highly
conserved structures present in many different microorganisms, known
as pathogen-associated molecular patterns. Recent studies have illustrated
that gd-Tcells and NK-T cells participate in natural immunity alongside
the classical cellular components such as neutrophils, macrophages
and NK cells. In leukocytes, chemotaxins activate phosphatidylinositol-3-kinase-γamma
(PI3Kγ), which synthetizes phosphatidylinositol-3,4,5-triphosphat
(PIP3). This lipid is further metabolised by SH2-containing inositol-5-phosphatase-1
(SHIP-1) to phosphatidylinositol-3.4-bisphosphate (PI3,4P2).
Moreover there is well evidence that PI3Kγ is also a protein kinase
and functions as an adaptor protein. The intention of this project
is the comparative study of upstream and downstream PI3Kγ/SHIP-1
signalling pathways in γδT-cells and NK-T cells, in order to highlight
the importance of this cascade in the immune system. For this approach
biochemical analyses (e.g. phospholipid measurements and Akt, Rac,
or Rho activation, between other molecules), macrocomplex formation
(e.g. immune precipitation, lipid rafts experiments, mass spectrometry),
cell studies (cytokine production, growth factor release, secretion
of matrix-metalloproteinases, cytotoxicity) and animal experiments
(e.g.infection with Escherichia coli) will be performed in PI3Kγ
-/- and SHIP-1 -/- mice.
Our present proposal integrates different biological aspects.
On one side, it is related to the study of the innate immune, one
of the most important mechanisms necessary for the maintainance
of the life, since its main objective is to gain fundamental knowledge
about the 3-phospholipid metabolism in immune cells, in order to
better understand their patho-and physiological consequences. On
the other hand, PI3Kγ as well as SHIP represent, between others,
a novel feature into the classical protein field. These proteins,
as well as some of their downstream adaptors, show a high plasticity
due to their multifunctionality, e.g. acting as enzymes or adaptor
proteins, which allows a larger range of pharmacological intervention
strategies, in order to modulate the immune reactions, as well as
other biological processes.
Publications:
- Lagadari M, Truta-Feles K, Lehmann K, Berod L, Ziemer M, Idzko M, Barz D, Kamradt T, Maghazachi AA, Norgauer J (2009) Lysophosphatidic acid inhibits
the cytotoxic activity of NK cells: involvement of Gs protein-mediated signaling. Int Immunol 21(6), 667-677.
- Lagadari M, Lehmann K, Ziemer M, Truta-Feles K, Berod L, Idzko M, Barz D, Kamradt T, Maghazachi AA, Norgauer J (2009)
Sphingosine-1-phosphate inhibits the cytotoxic activity of NK cells via Gs protein-mediated signalling. Int J Oncol 34(1), 287-294.
- Bagi ÉE, Tóth K, Truta-Feles K, Lénárd L (2005) Angiotensinerg regulation of salt hunger in the zona incerta
of rat brain. Acta Phys Hung 92, 237-239.
- Bagi ÉE, Truta-Feles K, Tóth K, Lénárd L (2004) Angiotensinergic
regulation of water and salt intake in the zona incerta and amygdala. Acta Phys Hung 91, 271-272.
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