title: Induction of Raf kinase inhibitor protein contributes to macrophage differentiation.
abstract: Differential gene expression analysis of human blood monocytes has identified the Raf kinase inhibitor protein (RKIP) as a continuously upregulated gene in macrophage and dendritic cell maturation. Using realtime RT-PCR and Western blot analysis we were able to confirm the initial DNA-microarray findings of RKIP induction on mRNA and protein levels. RKIP upregulation in primary cells and overexpression in THP-1 cells did not alter ERK activity but strongly reduced the amount of the NFkappaB subunit p65 in the nucleus. mRNA levels and cell surface expression of maturation markers including the integrin CD11c and the scavenger receptor CD36 were significantly increased in RKIP transfected THP-1 cells. Our data show for the first time that RKIP is upregulated during macrophage and dendritic cell differentiation on mRNA and protein levels and we conclude that RKIP contributes to the monocytic differentiation process via inhibition of the NFkappaB signaling cascade independent from the canonical Ras/Raf/MEK/ERK pathway.
authors.affiliation: Institute of Clinical Chemistry, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
authors.forename: Marion M
authors.initials: MM
authors.lastname: Schuierer
authors.forename: Ursula
authors.initials: U
authors.lastname: Heilmeier
authors.forename: Alfred
authors.initials: A
authors.lastname: Boettcher
authors.forename: Peter
authors.initials: P
authors.lastname: Ugocsai
authors.forename: Anja K
authors.initials: AK
authors.lastname: Bosserhoff
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.forename: Thomas
authors.initials: T
authors.lastname: Langmann
mesh_terms: D000727:Androgen-Binding Protein / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010586:Phagocytes / Q000166:cytology / Q000378:metabolism; D049488:Phosphatidylethanolamine Binding Protein
chemical_list: D000727:Androgen-Binding Protein; D016328:NF-kappa B; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein