HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active ribotoxin deoxynivalenol

Choi, Hye Jin; Yang, Hyun; Park, Seong Hwan; Moon, Yuseok

doi:10.1016/j.taap.2009.06.023

Cited by 43 publications

(43 citation statements)

References 38 publications

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“…Such an extended period of ATF3 expression thus triggered pathways that regulate p65 expression in response to Nod2 ligand. According to our previous study, ribosomal inactivation can enhance the transient cytosolic release of HuR protein (42). However, chronically induced ATF3 expression by ribosomal inactivation contributed to the nuclear entrapment of HuR protein via direct interaction with ATF3, which in turn caused the destabilization of p65 mRNA in the current study.…”

Section: Discussionmentioning

confidence: 45%

Novel Regulatory Action of Ribosomal Inactivation on Epithelial Nod2-Linked Proinflammatory Signals in Two Convergent ATF3-Associated Pathways

Park

Hun

Choi

et al. 2013

The Journal of Immunology

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In response to excessive nucleotide-binding oligomerization domain–containing protein 2 (Nod2) stimulation caused by mucosal bacterial components, gut epithelia need to activate regulatory machinery to maintain epithelial homeostasis. Activating transcription factor 3 (ATF3) is a representative regulator in the negative feedback loop that modulates TLR-associated inflammatory responses. In the current study, the regulatory effects of ribosomal stress-induced ATF3 on Nod2-stimulated proinflammatory signals were assessed. Ribosomal inactivation caused persistent ATF3 expression that in turn suppressed proinflammatory chemokine production facilitated by Nod2. Decreased chemokine production was due to attenuation of Nod2-activated NF-κB and early growth response protein 1 (EGR-1) signals by ATF3. However, the underlying molecular mechanisms involve two convergent regulatory pathways. Although ATF3 induced by ribosomal inactivation regulated Nod2-induced EGR-1 expression epigenetically through the recruitment of histone deacetylase 1, NF-κB regulation was associated with posttranscriptional regulation by ATF3 rather than epigenetic modification. ATF3 induced by ribosomal inactivation led to the destabilization of p65 mRNA caused by nuclear entrapment of transcript-stabilizing human Ag R protein via direct interaction with ATF3. These findings demonstrate that ribosomal stress-induced ATF3 is a critical regulator in the convergent pathways between EGR-1 and NF-κB, which contributes to the suppression of Nod2-activated proinflammatory gene expression.

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Section: Discussionmentioning

confidence: 45%

Novel Regulatory Action of Ribosomal Inactivation on Epithelial Nod2-Linked Proinflammatory Signals in Two Convergent ATF3-Associated Pathways

Park

Hun

Choi

et al. 2013

The Journal of Immunology

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“…7A). In addition, previous studies conducted by our group suggest that mucosal ribosomal stress plays a critical role in mRNA stabilization by triggering HuR translocation from nuclei to the cytoplasm, where it forms stable complexes with mRNAs containing AU-rich elements (57). In this study, we examined the involvement of HuR protein in SOCS3 mRNA stabilization by ribosomal stress; as expected, suppression of HuR expression retarded SOCS3 mRNA superinduction by cotreatment with IFN-g and ribosomal insulting agent in human intestinal epithelial cells (Fig.…”

Section: Ribosomal Insults Suppress Jak2-linked Baff Expression Via Smentioning

confidence: 81%

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

Hun

Choi

Kim

et al. 2013

The Journal of Immunology

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Although the activation of B cells in the gastrointestinal tract is of great importance in the context of immunity to pathogens and mucosal inflammatory diseases, little is known about the mechanisms responsible for the local activation of B cells in the subepithelial area of the intestine. Epithelium-derived BAFF is the major modulator of B cell development and Ig class switching. The present study was performed to address the molecular mechanism of BAFF expression in gut epithelial cells in the presence of proinflammatory stimuli. Inflammation-induced BAFF expression in mucosal epithelial cells might be responsible for diverse mucosa-associated diseases linked to intestinal inflammation and autoimmunity. Although BAFF was marginally expressed in unstimulated epithelial cells, BAFF mRNA was significantly upregulated by proinflammatory IFN-γ. Furthermore, IFN-γ triggered JAK/STAT1 signals via the cytokine receptor, which contributed to epithelial BAFF upregulation. In terms of signaling intervention, ribosomal insult attenuated IFN-γ–activated JAK/STAT signal transduction and subsequent BAFF induction in gut epithelial cells. Ribosomal insults led to the superinduction of SOCS3 by enhancing its mRNA stability via HuR RNA-binding protein. Upregulated SOCS3 then contributed to the blocking of the JAK/STAT-linked signal, which mediated BAFF suppression by ribosomal stress. All of these findings show that ribosomal stress–induced SOCS3 plays a novel regulatory role in epithelial BAFF production, suggesting that epithelial ribosomal dysfunction in association with SOCS3 may be a promising therapeutic point in BAFF-associated human mucosal diseases.

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“…The mechanism of growth faltering remains unclear. At higher doses used in some animal models this may reflect DON induced food rejection; though at more moderate exposures it may reflect poor uptake and retention of nutrients due to DON induced damage and inflammation of the intestinal mucosa (Bouhet and Oswald 2005;Choi et al 2009;Pinton et al 2009). …”

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confidence: 99%

Deoxynivalenol exposure assessment in a cohort of pregnant women from Bradford, UK

Hepworth

Hardie

Fraser

et al. 2012

Food Additives & Contaminants: Part A

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HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active ribotoxin deoxynivalenol

Cited by 43 publications

References 38 publications

Novel Regulatory Action of Ribosomal Inactivation on Epithelial Nod2-Linked Proinflammatory Signals in Two Convergent ATF3-Associated Pathways

Novel Regulatory Action of Ribosomal Inactivation on Epithelial Nod2-Linked Proinflammatory Signals in Two Convergent ATF3-Associated Pathways

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

Deoxynivalenol exposure assessment in a cohort of pregnant women from Bradford, UK

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