Inflammatory Cytokine Production by Human Neutrophils Involves C/EBP Transcription Factors

Cloutier, Alexandre; Guindi, Chantal; Larivée, Pierre; Dubois, Claire M.; Amrani, Abdelaziz; McDonald, Patrick P.

doi:10.4049/jimmunol.182.1.563

Cited by 95 publications

(79 citation statements)

References 56 publications

(72 reference statements)

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“…shown that C/EBP␤ plays an important role in regulating inflammatory responses in many different cell types (40,41). Similar to adipose tissue, the liver from WT mice on HFD showed a doubling of C/EBP␤ protein expression ( Fig.…”

Section: C/ebp␤ Controls Pro-inflammatory Gene Expression and Insulinmentioning

confidence: 88%

CCAAT/Enhancer-binding Protein β (C/EBPβ) Expression Regulates Dietary-induced Inflammation in Macrophages and Adipose Tissue in Mice

Rahman

Janssen

Choudhury

et al. 2012

Journal of Biological Chemistry

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Background: Role of CCAAT/enhancer-binding protein ␤ in obesity-induced inflammation remains unexplored. Results: Bone marrow-chimeric mice studies show that C/EBP␤ deletion regulates dietary-induced systemic inflammation and insulin resistance. Conclusion: C/EBP␤ expression in response to palmitate or high-fat diet controls transcriptional regulatory networks in macrophages and adipocytes critical for inflammation, lipid metabolism, and insulin resistance. Significance: Attenuating C/EBP␤ is an attractive target for ameliorating nutrition-induced inflammation.

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Section: C/ebp␤ Controls Pro-inflammatory Gene Expression and Insulinmentioning

confidence: 88%

CCAAT/Enhancer-binding Protein β (C/EBPβ) Expression Regulates Dietary-induced Inflammation in Macrophages and Adipose Tissue in Mice

Rahman

Janssen

Choudhury

et al. 2012

Journal of Biological Chemistry

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“…Importantly, the transcription factor activity associated with interferon and pathogen-associated molecular pattern (PAMP) receptors (Stat1, IRF3, and IRF7) was observed early (day 1 to 3 p.e.) during infection, while the activation of NF-B/REL, activator protein 1 (AP-1), and C/EBP, which are associated with regulating the production of inflammatory mediators in immune cells (31), showed a later upregulation (day 5 to 7 p.e. ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptional Profiling of the Immune Response to Marburg Virus Infection

Connor

Yen

Caballero

et al. 2015

J Virol

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Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCEMarburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the immune cells circulating in the blood of infected primates respond following exposure to Marburg virus. Our results show that there are three discernible stages of response to infection that correlate with presymptomatic, early, and late symptomatic stages of infection, a response format similar to that seen following challenge with other hemorrhagic fever viruses. In contrast to the ability of the virus to block innate immune signaling in vitro, the earliest and most sustained response is an interferon-like response. Our analysis also identifies a number of cytokines that are transcriptionally upregulated during late stages of infection and suggest that there is a Th2-skewed response to infection. When correlated with companion data describing the animal model from which our samples were collected, our results suggest that the innate immune response may contribute to overall pathogenesis.

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“…In addition to their classical functions, these professional phagocytes also generate a host of cytokines and chemokines that condition the progression of the inflammatory reaction and the subsequent onset of an immune response (1-4). We and others have shown that the production of inflammatory cytokines by neutrophils involves various signaling pathways, including the p38 MAPK, MEK/ERK, PI3K, and IKK/IkB cascades (5)(6)(7)(8), leading to transcriptional activation, in good part via members of the NF-kB and C/EBP families of transcription factors (5,7,9). By contrast, the JNK/AP-1 axis does not seem to contribute to cytokine production in neutrophils (7,10,11).…”

mentioning

confidence: 99%

Activation of TAK1 by Chemotactic and Growth Factors, and Its Impact on Human Neutrophil Signaling and Functional Responses

Sylvain-Prévost

Ear

Simard

et al. 2015

The Journal of Immunology

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The MAP3 kinase, TAK1, is known to act upstream of IKK and MAPK cascades in several cell types, and is typically activated in response to cytokines (e.g., TNF, IL-1) and TLR ligands. In this article, we report that in human neutrophils, TAK1 can also be activated by different classes of inflammatory stimuli, namely, chemoattractants and growth factors. After stimulation with such agents, TAK1 becomes rapidly and transiently activated. Blocking TAK1 kinase activity with a highly selective inhibitor (5z-7-oxozeaenol) attenuated the inducible phosphorylation of ERK occurring in response to these stimuli but had little or no effect on that of p38 MAPK or PI3K. Inhibition of TAK1 also impaired MEKK3 (but not MEKK1) activation by fMLF. Moreover, both TAK1 and the MEK/ERK module were found to influence inflammatory cytokine expression and release in fMLF- and GM-CSF–activated neutrophils, whereas the PI3K pathway influenced this response independently of TAK1. Besides cytokine production, other responses were found to be under TAK1 control in neutrophils stimulated with chemoattractants and/or GM-CSF, namely, delayed apoptosis and leukotriene biosynthesis. Our data further emphasize the central role of TAK1 in controlling signaling cascades and functional responses in primary neutrophils, making it a promising target for therapeutic intervention in view of the foremost role of neutrophils in several chronic inflammatory conditions.

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Inflammatory Cytokine Production by Human Neutrophils Involves C/EBP Transcription Factors

Cited by 95 publications

References 56 publications

CCAAT/Enhancer-binding Protein β (C/EBPβ) Expression Regulates Dietary-induced Inflammation in Macrophages and Adipose Tissue in Mice

CCAAT/Enhancer-binding Protein β (C/EBPβ) Expression Regulates Dietary-induced Inflammation in Macrophages and Adipose Tissue in Mice

Transcriptional Profiling of the Immune Response to Marburg Virus Infection

Activation of TAK1 by Chemotactic and Growth Factors, and Its Impact on Human Neutrophil Signaling and Functional Responses

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