TNFα‐induced ATF3 expression is bidirectionally regulated by the JNK and ERK pathways in vascular endothelial cells

Inoue, Kōichi; Zama, Takeru; Kamimoto, Takeyuki; Aoki, Ryoko; Ikeda, Yasuo; Kimura, Hiroshi; Hagiwara, Masatoshi

doi:10.1111/j.1356-9597.2004.00707.x

Cited by 71 publications

(56 citation statements)

References 51 publications

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“…In the absence of Fyn, its Fc⑀RI-dependent expression was reduced by 5.3-fold. The early response genes ATF3 and AP-1 are transcription factors whose expression is dependent on JNK activity (15,57). Thus, the loss of their Fc⑀RI-mediated expression is consistent with the observed defect in JNK activation in Fyn-deficient BMMC.…”

Section: Discussionsupporting

confidence: 70%

“…Of the cell surface Ag genes, Thy-1 (5.8-fold), transferrin receptor (4.9-fold), and the ADP-ribosyl cyclase-bone stromal cell Ag (BST)-1 (4.6-fold) were most significantly reduced in expression. Of the transcription factors, activated transcription factor (ATF)-3 (5.6-fold), a member of the CREB/ATF family of transcription factors induced by JNK (15), and SnoN (5.5-fold), a negative regulator of TGF-␤ signaling (16), were most affected by Fyn deficiency. The induction of IB␣, which is required for sequestering NF-B in the cytosol (17), was also found to be defective (3.2-fold).…”

Section: Altered Gene Expression Upon Fc⑀ri Stimulation Of Fyn-deficimentioning

confidence: 99%

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Impaired FcεRI-Dependent Gene Expression and Defective Eicosanoid and Cytokine Production as a Consequence of Fyn Deficiency in Mast Cells

Gomez

González-Espinosa

Odom

et al. 2005

The Journal of Immunology

106

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Fyn kinase is a key contributor in coupling FcεRI to mast cell degranulation. A limited macroarray analysis of FcεRI-induced gene expression suggested potential defects in lipid metabolism, eicosanoid and glutathione metabolism, and cytokine production. Biochemical analysis of these responses revealed that Fyn-deficient mast cells failed to secrete the inflammatory eicosanoid products leukotrienes B4 and C4, the cytokines IL-6 and TNF, and chemokines CCL2 (MCP-1) and CCL4 (MIP-1β). FcεRI-induced generation of arachidonic acid and normal induction of cytokine mRNA were defective. Defects in JNK and p38 MAPK activation were observed, whereas ERK1/2 and cytosolic phospholipase A2 (S505) phosphorylation was normal. Pharmacological studies revealed that JNK activity was associated with generation of arachidonic acid. FcεRI-mediated activation of IκB kinase β and IκBα phosphorylation and degradation was defective resulting in a marked decrease of the nuclear NF-κB DNA binding activity that drives IL-6 and TNF production in mast cells. However, not all cytokine were affected, as IL-13 production and secretion was enhanced. These studies reveal a major positive role for Fyn kinase in multiple mast cell inflammatory responses and demonstrate a selective negative regulatory role for certain cytokines.

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Section: Discussionsupporting

confidence: 70%

Section: Altered Gene Expression Upon Fc⑀ri Stimulation Of Fyn-deficimentioning

confidence: 99%

Impaired FcεRI-Dependent Gene Expression and Defective Eicosanoid and Cytokine Production as a Consequence of Fyn Deficiency in Mast Cells

Gomez

González-Espinosa

Odom

et al. 2005

The Journal of Immunology

106

View full text Add to dashboard Cite

show abstract

“…We also assessed the association between ATF3 upregulation and JNK phosphorylation. JNK belongs to a subset of MAPKs (a key cellular oxidative stress response pathway), thought to be upstream of the ATF3 signaling pathway, and has been previously shown to be an initiator of the ATF3 signaling cascade via transcriptional regulation (58). However, in contrast to our previous experiments in aortic endothelium, There is now significant clinical and epidemiologic data available pointing to the strong association of hyperlipidemia, as well as obesity, diabetes, and hypertension, in the development and possible causation of dementia.…”

Section: Discussionmentioning

confidence: 99%

Lipotoxic brain microvascular injury is mediated by activating transcription factor 3-dependent inflammatory and oxidative stress pathways

Aung¹,

Altman²,

Nyunt³

et al. 2016

Journal of Lipid Research

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Vascular cognitive impairment (VCI), a form of dementia caused by cerebrovascular disease, accounts for nearly 20% of cognitive dysfunction in the United States, and yet our understanding of the cerebrovascular disease processes underlying this dysfunction remains limited (1). Our understanding of vascular pathology in atherosclerotic cardiovascular disease (ASCVD) and the systemic circulation is more advanced and suggests important avenues of investigation, given the overlap of risk factors and epidemiology between ASCVD and cerebrovascular disease (2).Epidemiological evidence suggests a diet high in saturated fat and cholesterol negatively affects the health of the vasculature and contributes to the detrimental inflammatory injury that occurs in ASCVD and cerebrovascular disease (3-8). Studies also suggest that high levels of saturated fats and cholesterol contribute to the risk of developing VCI (9-14). Chronic intermittent vascular injury, as occurs over the course of decades of consumption of highfat meals, may significantly contribute to the long-term

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“…ATF3 expression is modulated by a wide variety of compounds including NSAIDs (29,38), genotoxic agents (ionizing radiation, UV radiation, and methyl methanesulfonate; ref. 42), peroxisome proliferator-activated receptor ligands (43), dietary compounds with cytotoxic activity and documented anticancer properties (34,44), anticancer drugs (35,36), and growth factors (45,46). The mechanisms of regulation for ATF3 are as diverse as the compounds that regulate ATF3 (for a review, see ref.…”

Section: Discussionmentioning

confidence: 99%

The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3)

Bottone

Moon

Kim

et al. 2005

Molecular Cancer Therapeutics

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We previously showed that nonsteroidal anti-inflammatory drugs (NSAID) such as sulindac sulfide, which has chemopreventive activity, modulate the expression of several genes detected by microarray analysis. Activating transcription factor 3 (ATF3) was selected for further study because it is a transcription factor involved in cell proliferation, apoptosis, and invasion, and its expression is repressed in human colorectal tumors as compared with normal adjacent tissue. In this report, we show that ATF3 mRNA and protein expression are up-regulated in HCT-116 human colorectal cancer cells following treatment with NSAIDs, troglitazone, diallyl disulfide, and resveratrol. To ascertain the biological significance of ATF3, we overexpressed full-length ATF3 protein in the sense and antisense orientations. Overexpression of ATF3 in the sense orientation decreased focus formation in vitro and reduced the size of mouse tumor xenografts by 54% in vivo. Conversely, overexpression of antisense ATF3 was protumorigenic in vitro, however, not in vivo. ATF3 in the sense orientation did not modulate apoptosis, indicating another mechanism is involved. With microarray analysis, several genes relating to invasion and metastasis were identified by ATF3 overexpression and were confirmed by real-time reverse transcription-PCR, and several of these genes were modulated by sulindac sulfide, which inhibited invasion in these cells. Furthermore, overexpression of ATF3 inhibited invasion to a similar degree as sulindac sulfide treatment, whereas antisense ATF3 increased invasion. In conclusion, ATF3 represents a novel mechanism in which NSAIDs exert their anti-invasive activity, thereby linking ATF3 and its gene regulatory activity to the biological activity of these compounds. [Mol Cancer Ther 2005;4(5):693 -703]

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TNFα‐induced ATF3 expression is bidirectionally regulated by the JNK and ERK pathways in vascular endothelial cells

Cited by 71 publications

References 51 publications

Impaired FcεRI-Dependent Gene Expression and Defective Eicosanoid and Cytokine Production as a Consequence of Fyn Deficiency in Mast Cells

Impaired FcεRI-Dependent Gene Expression and Defective Eicosanoid and Cytokine Production as a Consequence of Fyn Deficiency in Mast Cells

Lipotoxic brain microvascular injury is mediated by activating transcription factor 3-dependent inflammatory and oxidative stress pathways

The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3)

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