The Rel subunit of NF-kappa B-like transcription factors is a positive and negative regulator of macrophage gene expression: Distinct roles for Rel in different macrophage populations
- Author(s)
- Grigoriadis, G; Zhan, YF; Grumont, RJ; Metcalf, D; Handman, E; Cheers, C; Gerondakis, S;
- Details
- Publication Year 1996-12-16,Volume 15,Issue #24,Page 7099-7107
- Journal Title
- EMBO JOURNAL
- Publication Type
- Journal Article
- Abstract
- 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-kappa B 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.
- Publisher
- OXFORD UNIV PRESS
- Keywords
- TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; MURINE CUTANEOUS LEISHMANIASIS; DNA-BINDING SUBUNIT; C-REL; FACTOR-ALPHA; MICE LACKING; COOPERATIVE INTERACTION; MOLECULAR-CLONING; HUMAN-MONOCYTES
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Creation Date: 1996-12-16 12:00:00