Visit our Expo - Redox and Inflammation signaling 2012

VIII. Inflammation specific signaling Poster VIII, 8
Specific contribution of the signalling pathways NF-kappaB and PI3K / mTOR on the
gene expression profile of LPS stimulated murine macrophages
Sofia Dos Santos1, Anne-Isabelle Delattre, Françoise de Longueville2 and Martine
Raes1
1Laboratory of Biochemistry and Cellular Biology, University of Namur (F.U.N.D.P.),
Rue de Bruxelles, 61, 5000 Namur, Belgium. Email : martine.raes@fundp.ac.be,
2Eppendorf Array Technologies, Rue du Séminaire, 20a, 5000 Namur, Belgium.
Inflammation is the first response of the immune system to a variety of external or internal
insults, such as infectious agents, physical injury, hypoxia, or pathological processes.
In this study, we have simulated an inflammatory response by incubating RAW264.7 murine
macrophages with LPS (lipopolysaccharide), a major component of the outer membrane of
Gram-negative bacteria. The DNA microarray "DualChipTM Mouse Inflammation"
(Eppendorf) was used to characterize the gene expression profiles of LPS-stimulated
macrophages in the presence or not of BAY 11-7082 (a specific inhibitor of NF-kappaB) or
LY294002 (a specific inhibitor of the PI3K / mTOR pathway).
NF-kappaB is known to be a key transcription factor in the response to inflammation, but
little is known about the specific contribution of the PI3K / mTOR pathway in LPS signalling.
Results suggest a particularly important role for the transcription factor NF-kappaB, as
expected, but to a lesser extent the PI3K pathway is also involved. Differences between BAY
11-7082 and LY294002 were underlined. For example, genes encoding the PAF receptor,
PAI-1, PLA2 (group V), IL13 receptor (alpha 2) and GTP cyclohydrolase 1, which were upregulated
after LPS treatment, were mainly repressed by LY294002.
NF-kappaB plays an important role in the macrophage response to LPS, but we also have
shown that the PI3K pathway partially contributes to it. Further experiments with the specific
inhibitor of mTOR (rapamycin) will provide more information on the specific contribution of
the PI3K / mTOR pathway in the inflammatory response in LPS stimulated macrophages.
S. Dos Santos is a Research Fellow of FNRS (Fonds National de la Recherche Scientifique,
Brussels, Belgium).
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