Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual-specificity Phosphatase 1 (DUSP1)

Shah, Suharsh; Mostafa, Mahmoud; McWhae, Andrew; Traves, Suzanne L.; Newton, Robert

doi:10.1074/jbc.m115.697599

Cited by 27 publications

(34 citation statements)

References 65 publications

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“…After 1 h of IL1B, DUSP1 protein was induced, and this was enhanced by dexamethasone ( Fig. 10A) (22,23,27). In previous studies dexamethasone, IL1B, and IL1B plus dexamethasone showed no effect on the expression of total ERK (22) and total p38 (36), and Western blotting for total JNK also confirms this for JNK (data not shown).…”

Section: Effect Of Dusp1 Silencing On Mapks Irf1supporting

confidence: 70%

“…Turning to the actions of dexamethasone, we confirm that IL1B-induced expression of DUSP1 is enhanced by dexamethasone to reduce MAPK phosphorylation (23,27) (Fig. 12C).…”

Section: Negative Regulation Of Irf1 By Mapkssupporting

confidence: 59%

“…Furthermore, because glucocorticoids induce DUSP1 expression, this mechanism could contribute to glucocorticoid insensitivity. These concepts are explored using pulmonary A549 cells as a model of primary human bronchial epithelial cells, in which DUSP1 is induced by glucocorticoids and inflammatory gene expression is induced by IL1B and repressed by glucocorticoids (22,23,27).…”

mentioning

confidence: 99%

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DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes

Shah

King

Mostafa

et al. 2016

Journal of Biological Chemistry

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Although the mitogen-activated protein kinase (MAPK) phosphatase, DUSP1, mediates dexamethasone-induced repression of MAPKs, 14 of 46 interleukin-1␤ (IL1B)-induced mRNAs were significantly enhanced by DUSP1 overexpression in pulmonary A549 cells. These include the interferon regulatory factor, IRF1, and the chemokine, CXCL10. Of these, DUSP1-enhanced mRNAs, 10 including CXCL10, were IRF1-dependent. MAPK inhibitors and DUSP1 overexpression prolonged IRF1 expression by elevating transcription and increasing IRF1 mRNA and protein stability. Conversely, DUSP1 silencing increased IL1B-induced MAPK phosphorylation while significantly reducing IRF1 protein expression at 4 h. This confirms a regulatory network whereby DUSP1 switches off MAPKs to maintain IRF1 expression. There was no repression of IRF1 expression by dexamethasone in primary human bronchial epithelial cells, and in A549 cells IL1B-induced IRF1 protein was only modestly and transiently repressed. Although dexamethasone did not repress IL1B-induced IRF1 protein expression at 4 -6 h, silencing of IL1B plus dexamethasone-induced DUSP1 significantly reduced IRF1 expression. IL1B-induced expression of CXCL10 was largely insensitive to dexamethasone, whereas other DUSP1-enhanced, IRF1-dependent mRNAs showed various degrees of repression. With IL1B plus dexamethasone, CXCL10 expression was also IRF1-dependent, and expression was reduced by DUSP1 silencing. Thus, IL1B plus dexamethasone-induced DUSP1 maintains expression of IRF1 and the IRF1-dependent gene, CXCL10. This is supported by chromatin immunoprecipitation showing IRF1 recruitment to be essentially unaffected by dexamethasone at the CXCL10 promoter or at the promoters of more highly repressed IRF1-dependent genes. Since IRF1-dependent genes, such as CXCL10, are central to host defense, these data may help explain the reduced effectiveness of glucocorticoids during asthma exacerbations.Inhaled glucocorticoids are referred to clinically as inhaled corticosteroids and bind to the glucocorticoid receptor (GR 2 ; NR3C1). These drugs suppress inflammatory gene expression and are a mainstay in the treatment of asthma (1). However, poor responsiveness to inhaled corticosteroid therapy by asthmatics with neutrophilic inflammation or viral infections and by individuals with chronic obstructive pulmonary disease (COPD) necessitates high, often oral, doses of glucocorticoid (1-3). This, if maintained over prolonged periods, may lead to contraindications, including osteoporosis, muscle wasting, increased blood glucose, weight gain, and suppression of the hypothalamic-pituitary-adrenal axis (4). Thus, an unmet clinical need exists to improve the therapeutic ratio of glucocorticoids in such disease situations.Airway epithelial cells release proinflammatory cytokines, chemokines, adhesion molecules, and inflammatory enzymes and play critical roles in asthma (5). Acting on the airway epithelium, glucocorticoids suppress the production of numerous epithelial-derived mediators, and this helps to reduce inflammatory cell re...

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Section: Effect Of Dusp1 Silencing On Mapks Irf1supporting

confidence: 70%

“…Turning to the actions of dexamethasone, we confirm that IL1B-induced expression of DUSP1 is enhanced by dexamethasone to reduce MAPK phosphorylation (23,27) (Fig. 12C).…”

Section: Negative Regulation Of Irf1 By Mapkssupporting

confidence: 59%

mentioning

confidence: 99%

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DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes

Shah

King

Mostafa

et al. 2016

Journal of Biological Chemistry

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“…2C, panel i). Thus, in A549 cells, DUSP1 silencing transiently hyper-activates IL1B-induced MAPKs and correspondingly increases ZFP36 expression (63) (Fig. 2C, panel ii).…”

Section: Incoherent Feedforward Control By Zfp36mentioning

confidence: 85%

“…ZFP36 induction occurs in many cells, including A549 epithelial and primary human airway smooth muscle cells (61,62). This requires p38 MAPK to constitute an incoherent feedforward loop with ZFP36 as a negative regulator of ARE-containing mRNAs, such as TNF (60,63) (Fig. 2C, panel i).…”

Section: Incoherent Feedforward Control By Zfp36mentioning

confidence: 99%

Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance

Newton

Shah

Altonsy

et al. 2017

Journal of Biological Chemistry

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Edited by Luke O'NeillInflammatory signals induce feedback and feedforward systems that provide temporal control. Although glucocorticoids can repress inflammatory gene expression, glucocorticoid receptor recruitment increases expression of negative feedback and feedforward regulators, including the phosphatase, DUSP1, the ubiquitin-modifying enzyme, TNFAIP3, or the mRNAdestabilizing protein, ZFP36. Moreover, glucocorticoid receptor cooperativity with factors, including nuclear factor-B (NF-B), may enhance regulator expression to promote repression. Conversely, MAPKs, which are inhibited by glucocorticoids, provide feedforward control to limit expression of the transcription factor IRF1, and the chemokine, CXCL10. We propose that modulation of feedback and feedforward control can determine repression or resistance of inflammatory gene expression toglucocorticoid.

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FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis

Huang

Luo

Huang

et al. 2022

The Kaohsiung J of Med Scie

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Hyperglycemia is the most important factor leading to the complications of type 2 diabetes mellitus (T2DM). The primary condition for the treatment of T2DM is to change the glucose and lipid metabolism disorders in the liver and other insulin-sensitive tissues. The current study aims to unearth the potential molecular mechanism of inhibiting liver gluconeogenesis to provide a new theoretical basis for the treatment of T2DM. High glucose (HG) induction of HepG2 cells followed by treatment with sequence-similar family 3 member D (FAM3D). Dual specificity phosphatases 1 (DUSP1), zinc finger protein 36 (ZFP36), salt-induced kinase 1 (SIK1), p-SIK1, posphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene and protein expression level were detected by quantitative real-time polymerase chain reaction and western blot. The PEPCK and G6Pase activities were detected by enzyme linked immunosorbent assay.Glucose production assay to determine glucose content. The RNA binding protein immunoprecipitation assay was used to detect the binding of ZFP36 to SIK1. FAM3D facilitated the expression of DUSP1 but suppressed the expression of gluconeogenesis-related factors in an HG environment. The expression of ZFP36 was up-regulated in an HG environment. ZFP36 could reverse the inhibition of gluconeogenesis caused by FAM3D. HG-induced upregulation of ZFP36 was downregulated by overexpression of DUSP1. ZFP36 bound to SIK1, and downregulation of ZFP36 promoted SIK1 expression and inhibits gluconeogenesis. Our study demonstrated FAM3D inhibited gluconeogenesis through the DUSP1/ ZFP36/SIK1 axis in an HG environment, which provided a new theoretical basis for exploring the pathogenesis and treatment strategy of T2DM.

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Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual-specificity Phosphatase 1 (DUSP1)

Cited by 27 publications

References 65 publications

DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes

DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes

Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance

FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis

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