Regulation of macrophage and neutrophil cell fates by the PU.1:C/EBPα ratio and granulocyte colony-stimulating factor

Dahl, Richard; Walsh, Jared P.; Lancki, David W.; Laslo, Peter; Iyer, Sangeeta R.; Singh, Harinder; Simon, M. Celeste

doi:10.1038/ni973

Cited by 341 publications

(370 citation statements)

References 40 publications

Supporting

Mentioning

351

Contrasting

Unclassified

Order By: Relevance

“…A similar model could be envisioned for CaMKIIγ, and CKLiK plus CaMKIIγ may be part of a complex signaling network that regulates both neutrophil differentiation and function. Precedence for this model is provided by two other regulators of hematopoiesis: the Src family kinase Lyn can positively and negatively regulate cytokine signaling in B-cells and in myeloid lineages, and concentrations of PU.1 determine whether it cooperates with or antagonizes the function of C/EBPα to regulate neutrophil maturation [42][43][44].…”

Section: Discussionmentioning

confidence: 99%

A cascade of Ca2+/calmodulin-dependent protein kinases regulates the differentiation and functional activation of murine neutrophils

Gaines

Lamoureux

Marisetty

et al. 2008

Experimental Hematology

View full text Add to dashboard Cite

Objective-The function of neutrophils as primary mediators of innate immunity depends on the activity of granule proteins and critical components of the NADPH oxidase complex. Expression of their cognate genes is regulated during neutrophil differentiation by a complex network of intracellular signaling pathways. In this study we have investigated the role of two members of the calcium/calmodulin-dependent protein kinase (CaMK) signaling cascade, CaMKI-like kinase (CKLiK) and CaMKKα, in regulating neutrophil differentiation and functional activation.Materials and Methods-Mouse myeloid cell lines were used to examine the expression of a CaMK cascade in developing neutrophils and to examine the effects of constitutive activation versus inhibition of CaMKs on neutrophil maturation.Results-Expression of CaMKKα was shown to increase during neutrophil differentiation in multiple cell lines, whereas expression of CKLiK increased as multipotent progenitors committed to promyelocytes but then decreased as cells differentiated into mature neutrophils. Expression of constitutively active CKLiKs did not affect morphologic maturation, but caused dramatic decreases in both respiratory burst responses and chemotaxis. This loss of neutrophil function was accompanied by reduced secondary granule and gp91 phox gene expression. The CaMK inhibitor KN93 attenuated cytokine-stimulated proliferative responses in promyelocytic cell lines, and inhibited the respiratory burst. Similar data were observed with the CaMKKα inhibitor, STO-609.Conclusions-Overactivation of a cascade of CaMKs inhibits neutrophil maturation, suggesting that these kinases play an antagonistic role during neutrophil differentiation, but at least one CaMK is required for myeloid cell expansion and functional activation.

show abstract

Section: Discussionmentioning

confidence: 99%

A cascade of Ca2+/calmodulin-dependent protein kinases regulates the differentiation and functional activation of murine neutrophils

Gaines

Lamoureux

Marisetty

et al. 2008

Experimental Hematology

View full text Add to dashboard Cite

show abstract

“…PU.1 is expressed in hemopoietic cells and is important for myeloid cell development and maturation and macrophage differentiation (27). PU.1-deficient mice completely lack macrophages and absence of PU.1 impairs myeloid cell differentiation (42,43). PU.1 is also important for osteoclast differentiation and maturation (43) and is present in microglia where it is significantly up-regulated during ischemic injury (44).…”

Section: Discussionmentioning

confidence: 99%

Corticotropin-Releasing Factor and the Urocortins Induce the Expression of TLR4 in Macrophages via Activation of the Transcription Factors PU.1 and AP-1

Tsatsanis¹,

Androulidaki²,

Alissafi³

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Corticotropin-releasing factor (CRF) augments LPS-induced proinflammatory cytokine production from macrophages. The aim of the present study was to determine the mechanism by which CRF and its related peptides urocortins (UCN) 1 and 2 affect LPS-induced cytokine production. We examined their role on TLR4 expression, the signal-transducing receptor of LPS. For this purpose, the murine macrophage cell line RAW 264.7 and primary murine peritoneal macrophages were used. Exposure of peritoneal macrophages and RAW 264.7 cells to CRF, UCN1, or UCN2 up-regulated TLR4 mRNA and protein levels. To study whether that effect occurred at the transcriptional level, RAW 264.7 cells were transfected with a construct containing the proximal region of the TLR4 promoter linked to the luciferase gene. CRF peptides induced activation of the TLR4 promoter, an effect abolished upon mutation of a proximal PU.1-binding consensus or upon mutation of an AP-1-binding element. Indeed, all three peptides promoted PU.1 binding to the proximal PU.1 site and increased DNA-binding activity to the AP-1 site. The effects of CRF peptides were inhibited by the CRF2 antagonist anti-sauvagine-30, but not by the CRF1 antagonist antalarmin, suggesting that CRF peptides mediated the up-regulation of TLR4 via the CRF2 receptor. Finally, CRF peptides blocked the inhibitory effect of LPS on TLR4 expression. In conclusion, our data suggest that CRF peptides play an important role on macrophage function. They augment the effect of LPS by inducing Tlr4 gene expression, through CRF2, via activation of the transcription factors PU.1 and AP-1.

show abstract

“…This differentiation regulation is dose-dependent; a high level of PU.1 expression favors differentiation to dendritic cells over differentiation to macrophages [106]. It also promotes macrophage differentiation more than granulocyte differentiation [107]. Conditional PU.1 deletion in adult mice showed that PU.1 was required by lymphoid and myeloid progenitors.…”

Section: Transcription Factors Regulating Hscsmentioning

confidence: 99%

Mechanisms of self-renewal in hematopoietic stem cells

Wang

Ema

2015

Int J Hematol

View full text Add to dashboard Cite

Regulation of macrophage and neutrophil cell fates by the PU.1:C/EBPα ratio and granulocyte colony-stimulating factor

Cited by 341 publications

References 40 publications

A cascade of Ca2+/calmodulin-dependent protein kinases regulates the differentiation and functional activation of murine neutrophils

A cascade of Ca2+/calmodulin-dependent protein kinases regulates the differentiation and functional activation of murine neutrophils

Corticotropin-Releasing Factor and the Urocortins Induce the Expression of TLR4 in Macrophages via Activation of the Transcription Factors PU.1 and AP-1

Mechanisms of self-renewal in hematopoietic stem cells

Contact Info

Product

Resources

About