The Rel subunit of NF-I?B-like transcription factors is a positive and negative regulator of macrophage gene expression: Distinct roles for Rel in different macrophage populations

George Grigoriadis, Yifan Zhan, Raelene Joy Grumont, Donald Metcalf, Emanuela Handman, Christina Cheers, Steven Demetrious Gerondakis

Research output: Contribution to journalArticleResearchpeer-review

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-I? (TNF-I?) 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-I? 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-I?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.
Original languageEnglish
Pages (from-to)7099 - 7107
Number of pages9
JournalEMBO Journal
Volume15
Issue number24
Publication statusPublished - 1996

Cite this

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title = "The Rel subunit of NF-I?B-like transcription factors is a positive and negative regulator of macrophage gene expression: Distinct roles for Rel in different macrophage populations",
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-I? (TNF-I?) 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-I? 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-I?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.",
author = "George Grigoriadis and Yifan Zhan and Grumont, {Raelene Joy} and Donald Metcalf and Emanuela Handman and Christina Cheers and Gerondakis, {Steven Demetrious}",
year = "1996",
language = "English",
volume = "15",
pages = "7099 -- 7107",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "EMBO Press",
number = "24",

}

The Rel subunit of NF-I?B-like transcription factors is a positive and negative regulator of macrophage gene expression: Distinct roles for Rel in different macrophage populations. / Grigoriadis, George; Zhan, Yifan; Grumont, Raelene Joy; Metcalf, Donald; Handman, Emanuela; Cheers, Christina; Gerondakis, Steven Demetrious.

In: EMBO Journal, Vol. 15, No. 24, 1996, p. 7099 - 7107.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The Rel subunit of NF-I?B-like transcription factors is a positive and negative regulator of macrophage gene expression: Distinct roles for Rel in different macrophage populations

AU - Grigoriadis, George

AU - Zhan, Yifan

AU - Grumont, Raelene Joy

AU - Metcalf, Donald

AU - Handman, Emanuela

AU - Cheers, Christina

AU - Gerondakis, Steven Demetrious

PY - 1996

Y1 - 1996

N2 - 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-I? (TNF-I?) 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-I? 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-I?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.

AB - 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-I? (TNF-I?) 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-I? 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-I?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.

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