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Publication : The Rel subunit of NF-kappaB-like transcription factors is a positive and negative regulator of macrophage gene expression: distinct roles for Rel in different macrophage populations.

First Author  Grigoriadis G Year  1996
Journal  EMBO J Volume  15
Issue  24 Pages  7099-107
PubMed ID  9003785 Mgi Jnum  J:37541
Mgi Id  MGI:84932 Citation  Grigoriadis G, et al. (1996) The Rel subunit of NF-kappaB-like transcription factors is a positive and negative regulator of macrophage gene expression: distinct roles for Rel in different macrophage populations. EMBO J 15(24):7099-107
abstractText  The role of Rel in the monocyte/macrophage lineage was examined in mice with an inactivated c-rel gene. Although the frequency of monocytic cells was normal in Rel-/- mice, we show that Rel serves distinct roles in regulating gene expression and immune effector function in different mature macrophage populations. Stimulated Rel-/- resident peritoneal macrophages produced higher than normal levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), but tumour necrosis factor-alpha (TNF-alpha) production was not induced. Diminished cytotoxic activity exhibited by resident Rel-/- macrophages was consistent with reduced nitric oxide production resulting from impaired up-regulation of inducible nitric oxide synthase expression. While a similar altered pattern of IL-6 and TNF-alpha expression was observed in stimulated Rel-/- peritoneal effusion macrophages, cytotoxic activity, nitric oxide, GM-CSF and G-CSF production by these cells was normal. The alternate regulation of certain genes in the two macrophage populations coincided with different patterns of nuclear Rel/NF-kappaB complexes expressed in normal resident and elicited cells. Collectively, these results establish that Rel is a positive or negative regulator of transcription in macrophages and that Rel has distinct roles in different macrophage populations.
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