Gene expression profiling of LPS-stimulated murine macrophages and role of the NF-kappaB and PI3K/mTOR signaling pathways.
Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, activates a broad spectrum of signaling pathways in immune cells. In this article, RAW264.7 cells have been stimulated for 4 h with 1 microg/mL of LPS in the presence or not of specific inhibitors of the NF-kappaB pathway (BAY 11-7082) and the PI3K pathway (LY294002). Gene expression profiles were characterized using the DNA microarray "Dual Chip Mouse Inflammation." This array monitors the expression of 233 genes encoding proteins playing a role in inflammation. Both signaling pathways exert an important role in the response to LPS, but they are not completely overlapping. For example, genes encoding the PAF receptor, PAI-1, PlA2 (group V), IL-13 receptor (alpha2), and GTP cyclohydrolase 1, were upregulated after LPS treatment, but this upregulation was counteracted by LY294002. The same was observed for BAY 11-7082: genes encoding the kit ligand, TLR2, or TNFRSF5 were mainly under the control of NF-kappaB. NF-kappaB plays an important role in the macrophage response to LPS, but we have also 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.
Dos Santos
S
S
Laboratory of Biochemistry and Cellular Biology, University of Namur (F.U.N.D.P.), Rue de Bruxelles, 61, 5000 Namur, Belgium.
Delattre
A-I
AI
De Longueville
F
F
Bult
H
H
Raes
M
M
D000818:Animals; D002867:Chromones / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D015854:Up-Regulation
D002867:Chromones; D008070:Lipopolysaccharides; D009025:Morpholines; D016328:NF-kappa B; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D013450:Sulfones; D058570:TOR Serine-Threonine Kinases; C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546843:mTOR protein, mouse