Post-transcriptional regulation of eotaxin by glucocorticoids (GC) and by interleukin (IL)-4

Heller, Nicola; Curry, Stephanie; Nickel, Renate; Plunkett, Beverly; Huang, S-K; Shyu, Ann‐Bin; Schleimer, R.P.; Stellato, Cristiana

doi:10.1016/s0091-6749(02)81603-7

Cited by 3 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding the cis-elements involved, acceleration of chemokine mRNA decay by GCs could be ARE dependent, as previously demonstrated for IFN-b and COX-2 [93,120]. Such elements may play a role in GC-induced eotaxin inhibition in airway epithelial cells, as GC treatment accelerated the decay of a reporter containing the ARE-bearing eotaxin 39-UTR [79]. The presence of AREs in the 39-UTR by itself is not always predictive of GC-mediated changes in chemokine mRNA turnover.…”

Section: Post-transcriptional Regulation Of Chemokines As Target Of Amentioning

confidence: 53%

“…On the contrary, the combination of TNF-a plus IL-4, which yields the strongest synergistic effect on eotaxin protein secretion [80], significantly increases the stability of eotaxin mRNA [55]. Such changes appear to be mediated by the 39-UTR of the CCL11 mRNA, as both the acceleration of mRNA decay induced by budesonide and the cytokine-induced increase in mRNA stability were reproduced using the transcriptional pulsing approach, in which the expression of a chimeric b-globin reporter mRNA bearing the CCL11 39-UTR was monitored in transfected National Institutes of Health 3T3 cells, following treatment with either budesonide or TNF-a plus IL-4 [55,79].…”

Section: Post-transcriptional Regulation Of Chemokine Expression: Todmentioning

confidence: 99%

See 1 more Smart Citation

The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy

Fan¹

2005

Eur Respir J

View full text Add to dashboard Cite

The aim of this review is to discuss recent advances in the understanding of the regulation of chemokine expression occurring during chronic inflammatory conditions, such as allergic diseases. The focus will be on current data, which suggest that post-transcriptional regulation plays a larger role in chemokine gene regulation than previously recognised. In particular, a growing body of data indicates that mechanisms controlling mRNA stability may be relevant in determining, or maintaining, the increased levels of chemokine gene expression in this context. Such regulatory pathways may be important targets of novel anti-inflammatory strategies.KEYWORDS: Allergy, chemokines, inflammation, post-transcriptional regulation, RNA stability BACKGROUND Since the 1980s, research on the superfamily of small, secreted proteins known as the chemokines has steadily grown into a research world of its own. It is now clearly established that these molecules play a central role in many homeostatic and pathological processes in human biology. Chiefly, chemokines shape the way in which the immune system responds to an inflammatory insult, by coordinating the recruitment, activation and homing of leukocytes during the different phases of both innate and adaptive inflammatory responses [1]. It is easy to envision how an alteration of chemokine expression or function might lead to the persistence of an inflammatory reaction well beyond its original purpose, therefore creating a key pathogenetic event for the establishment of chronic inflammation [2].

show abstract

Section: Post-transcriptional Regulation Of Chemokines As Target Of Amentioning

confidence: 53%

Section: Post-transcriptional Regulation Of Chemokine Expression: Todmentioning

confidence: 99%

The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy

Fan¹

2005

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…This article describes evidence that glucocorticoids have effects on post-transcriptional and nongenomic gene regulatory events that integrate with transcriptional regulation and are crucial in shaping gene expression during an inflammatory response. Some of the results of these studies have been previously reported in the form of an abstract (1).…”

mentioning

confidence: 96%

“…The 3Ј-UTR of CCL11 contains a tandem AUUUA sequence in a TA-rich stretch (21), indicating the potential for post-transcriptional regulation. Treatment with glucocorticoid significantly decreased the half-life of a heterologous reporter mRNA bearing the CCL11 3Ј-UTR, indicating that the effect of glucocorticoids was CCL11 3Ј-UTR-dependent, at least in part (1). Interestingly, the stabilizing effect of TNF-␣ plus IL-4 on CCL11 mRNA was reproducible upon cytokine challenge of cells transfected with the reporter construct containing the CCL11 3Ј-UTR (1), which is further evidence that this region is a point of convergence of regulatory signals with either pro-or antiinflammatory effect.…”

mentioning

confidence: 99%

Post-transcriptional and Nongenomic Effects of Glucocorticoids

Stellato¹

2004

Proceedings of the American Thoracic Society

159

121

View full text Add to dashboard Cite

The ability of glucocorticoids to interfere with post-transcriptional gene regulation has recently been recognized as a potentially important part of their anti-inflammatory property, and the mechanisms governing such activity are under active investigation. Several studies have shown that glucocorticoids can inhibit inflammatory signaling pathways known to control mRNA turnover and translation. Moreover, several glucocorticoid-sensitive determinants have been identified on mRNA molecules of inflammatory genes, and the RNA-binding factors interacting with them might constitute relevant glucocorticoid targets. Glucocorticoids also exert effects characterized as nongenomic, which occur within minutes of drug administration. The mechanisms of action of nongenomic glucocorticoid effects differ from the classical, transcription-dependent glucocorticoid action and involve the production of second-messenger molecules and activation of signal transduction pathways, either by the nuclear glucocorticoid receptor or by a membrane glucocorticoid receptor that has not yet been fully characterized. Ultimately, the discovery of novel pathways involved in mediating the actions of glucocorticoids should lead to improved targets for anti-inflammatory therapy.

show abstract

“…1). Furthermore, we previously showed that in airway epithelial cells, inhibition of eotaxin expression by glucocorticoids was due, at least in part, to acceleration of eotaxin mRNA decay through a 3ЈUTR-mediated mechanism (23,33). Moreover, combined treatment with TNF-␣ and IL-4 has been shown to affect the stability of mRNAs encoding other proinflammatory molecules such as VCAM-1 (34).…”

mentioning

confidence: 99%

Regulation of Eotaxin Gene Expression by TNF-α and IL-4 Through mRNA Stabilization: Involvement of the RNA-Binding Protein HuR

Atasoy

Curry

Silanes

et al. 2003

The Journal of Immunology

Self Cite

110

View full text Add to dashboard Cite

During inflammatory responses, a major posttranscriptional regulation of early response and inflammatory gene expression occurs through modulation of mRNA turnover. We report that two potent inducers of the CC chemokine eotaxin, TNF-α and IL-4, regulate its production in airway epithelial cells by increasing eotaxin mRNA stability. In experiments using the transcriptional inhibitor actinomycin D, eotaxin mRNA half-life was significantly prolonged by cell stimulation with TNF-α or IL-4, with the combination of the two cytokines being the most effective in extending the mRNA half-life. Involvement of the eotaxin 3′ untranslated region in the mRNA-stabilizing effect was tested by transient transfection of a construct expressing a chimeric transcript carrying a serum-inducible β-globin reporter linked to the eotaxin 3′ untranslated region. The half-life of the chimeric mRNA was markedly increased in cells stimulated with TNF-α and IL-4. Evidence that the mRNA-stabilizing protein HuR participated in the cytokine effect was obtained: first, HuR presence in the cytoplasm, believed to be required for HuR-mediated mRNA stabilization, increased in both transformed (BEAS-2B cell line) and primary bronchial epithelial cells following treatment with TNF-α and IL-4. Second, endogenous eotaxin mRNA was found to bind to HuR in vivo, as detected by immunoprecipitation of HuR-containing messenger ribonucleoprotein complexes followed by real-time RT-PCR analysis; such association increased after cell treatment with TNF-α and IL-4. Third, overexpression of HuR in BEAS-2B cells significantly increased the expression of eotaxin mRNA and protein. Our findings implicate mRNA stabilization in the cytokine-mediated increase in eotaxin expression and strongly suggest a role for HuR in this effect.

show abstract

Post-transcriptional regulation of eotaxin by glucocorticoids (GC) and by interleukin (IL)-4

Cited by 3 publications

References 0 publications

The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy

The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy

Post-transcriptional and Nongenomic Effects of Glucocorticoids

Regulation of Eotaxin Gene Expression by TNF-α and IL-4 Through mRNA Stabilization: Involvement of the RNA-Binding Protein HuR

Contact Info

Product

Resources

About