De novo synthesis of early growth response factor-1 is required for the full responsiveness of mast cells to produce TNF and IL-13 by IgE and antigen stimulation

Li, Bo; Power, Melanie R.; Lin, Tong‐Jun

doi:10.1182/blood-2005-09-3610

Cited by 46 publications

(73 citation statements)

References 47 publications

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“…EMSA was performed, as previously described (53). Briefly, probe labeling was accomplished by treatment with T4 kinase (Life Technologies, Burlington, ON, Canada) in the presence of 32 P adenosine triphosphate (Perkin Elmer, Waltham, MA).…”

Section: Nuclear Extract Preparation and Emsamentioning

confidence: 99%

Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Junkins

MacNeil

et al. 2013

The Journal of Immunology

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Respiratory tract infection with Pseudomonas aeruginosa is a common cause of hospitalization in immune-compromised individuals. However, the molecular mechanisms involved in the immune response to P. aeruginosa lung infection remain incompletely defined. In this study, we demonstrate that the regulator of calcineurin 1 (RCAN1) is a central negative regulator of inflammation in a mouse model of acute bacterial pneumonia using the opportunistic bacterial pathogen P. aeruginosa. RCAN1-deficient mice display greatly increased mortality following P. aeruginosa lung infection despite enhanced neutrophil recruitment and bacterial clearance. This mortality is associated with higher systemic levels of proinflammatory cytokines in RCAN1-deficient animals. These aberrant inflammatory responses coincide with increased transcriptional activity of proinflammatory RCAN1-target proteins NFAT and NF-κB. In addition, we reveal a novel regulatory role for RCAN1 in the ERK/STAT3 pathway both in vitro and in vivo, suggesting that aberrant STAT3 activity may significantly contribute to delayed resolution of inflammatory responses in our model. Together, these findings demonstrate that RCAN1 is a potent negative regulator of inflammation during respiratory tract infections.

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Section: Nuclear Extract Preparation and Emsamentioning

confidence: 99%

Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Junkins

MacNeil

et al. 2013

The Journal of Immunology

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“…EMSA was performed as previously described (18). The following synthesized double-stranded oligonucleotides (Sigma-Aldrich) were used: NF-kBbinding consensus sequences on mouse IL-6 promoter, 59-TTATCAAATG-TGGGATTTTCCCAT-39 and the mutant sequence, 59-TTATCAAATGTG-TTACCTTCCCAT-39; NFAT-binding consensus sequence on mouse IL-13 promoter, 59-AAGGTGTTTCCCCAAGCCTTTCCC-39 and the mutant sequence, 59-AAGGTGTCCATCCAAGCCTCCATC-39; and Egr2-binding consensus sequence on CCL1 promoter, 59-TCAGCCAGGACAGCTCCC-ACGTATTTTG-39 and the mutant sequence, 59-TCAGCCAGGACATATC-CCATATATTTTG-39 (italics indicate mutated bases).…”

Section: Electrophoretic Mobility Shift Assaymentioning

confidence: 99%

“…Immunofluorescence was as described previously (18), except samples were incubated overnight with anti-Egr2 Ab (16 mg/ml) or rabbit serum (Cedarlane) at 4˚C.…”

Section: Immunofluorescencementioning

confidence: 99%

“…The mouse Egr2 probe was prepared by PCR from the subtractive hybridization plasmid clone pCR4-TOPO 1F7 with M13 forward (220) and M13 reverse primers. Real-time quantitative PCR for Egr2 and Egr1 was performed and analyzed as previously described (18).…”

Section: Subtractive Hybridization Virtual Northern Analysis and Rementioning

confidence: 99%

“…For example, Egr2 is critical in the development and maturation of NKT cells as well as B and T cells (14,15) and is also an essential transcription factor in the nervous system, regulating peripheral nerve myelination as well as segmentation in hindbrain development (16,17). We have previously described the role of family member Egr1 in regulating the full responsiveness of cytokine production in FcεRI-activated mast cells (18)(19)(20); however, the role of Egr2 in mast cell activation has not been described.…”

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confidence: 99%

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Mast Cell FcεRI-Induced Early Growth Response 2 Regulates CC Chemokine Ligand 1–Dependent CD4+ T Cell Migration

MacNeil

Junkins

et al. 2013

The Journal of Immunology

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Mast cells are well positioned in host tissue for detecting environmental signals, including allergens, leading to activation of the high-affinity IgE receptor FcεRI, and initiating a signaling cascade that perpetuates the production of biologically potent mediators, including chemokines. We have identified a novel target of mast cell FcεRI activity in the transcription factor early growth response 2 (Egr2) and sought to characterize its function therein. Egr2 was transiently activated following FcεRI-mediated signaling, targeted the promoter of the chemokine CCL1, and was critical for allergen-induced mast cell CCL1 production. Egr2-deficient mast cells were incapable of directing CD4+ T cell migration via the CCL1–CCR8 axis. In a model of allergic asthma, reconstitution of mast cell–deficient mice with Egr2-deficient mast cells demonstrated that mast cell Egr2 was essential for migration of CD4+ T cells to the inflamed lung. These findings position Egr2 as a critical regulator of mast cell–directed CD4+ T cell migration.

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Mast cell transcription factors—Regulators of cell fate and phenotype

Tshori

Nechushtan

2012

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Transcription factors have a key role in mast cell differentiation and response of differentiated mast cells to external stimuli. During differentiation of progenitor cells to mast cells, a role for different GATA transcription factors in combination with PU.1 expression and downregulation of C/EBPα has been described. Notch pathway has been proposed to have a role in mast cell development. The microphthalmia-associated transcription factor expression is upregulated in later stages of mast cells differentiation, but it is not expressed in the closely related basophiles. In differentiated mast cells, there is a role for transcription factors both in determining the specific mast cell phenotype and in the response to immune stimuli such as IgE-Ag. A large number of transcription factors, including AP-1 family proteins, microphthalmia-associated transcription factor and STAT5, are modulated by these stimuli. These transcription factors and related protein modulators form a complex transcription factor network. They can form stimuli regulated specific heterodimers and common inhibitors can move from one protein to another. Transcription factors are the key regulators of mast cell physiology. Modulation of key transcription by such means as the therapeutic siRNA may hopefully allow us to modulate mast cell function, obtaining clinical benefit in a variety of diseases. This article is part of a Special Issue entitled: Mast cells in inflammation.

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De novo synthesis of early growth response factor-1 is required for the full responsiveness of mast cells to produce TNF and IL-13 by IgE and antigen stimulation

Cited by 46 publications

References 47 publications

Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Mast Cell FcεRI-Induced Early Growth Response 2 Regulates CC Chemokine Ligand 1–Dependent CD4+ T Cell Migration

Mast cell transcription factors—Regulators of cell fate and phenotype

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