Tristetraprolin down‐regulates IL‐17 through mRNA destabilization

Lee, Hyun Hee; Yoon, Nal Ae; Vo, Mai-Tram; Kim, Chae Won; Woo, Je Moon; Jeong, Hee; Cho, Young Woo; Lee, Byung Ju; Cho, Wha Ja; Park, Jeong Woo

doi:10.1016/j.febslet.2011.11.021

Cited by 54 publications

(37 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HuR is highly selective in its interaction with its cognate mRNA binding partners and has been described as an active participant in promoting mRNA stability2627. In contrast, TTP promotes mRNA degradation by destabilizing target transcripts282930. The acute inflammation elicited by DSS and SA treatments significantly suppressed both ANGPTL4 and TTP expression in ANGPTL4 +/+ littermates (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 95%

Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin

Phua

Sng

Tan

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Many gastrointestinal diseases exhibit a protracted and aggravated inflammatory response that can lead to hypercytokinaemia, culminating in extensive tissue damage. Recently, angiopoietin-like 4 (ANGPTL4) has been implicated in many inflammation-associated diseases. However, how ANGPTL4 regulates colonic inflammation remains unclear. Herein, we show that ANGPTL4 deficiency in mice (ANGPTL4−/−) exacerbated colonic inflammation induced by dextran sulfate sodium (DSS) or stearic acid. Microbiota was similar between the two genotypes prior DSS challenge. A microarray gene expression profile of the colon from DSS-treated ANGPTL4−/− mice was enriched for genes involved in leukocyte migration and infiltration, and showed a close association to inflamed ulcerative colitis (UC), whereas the profile from ANGPTL4+/+ littermates resembled that of non-inflamed UC biopsies. Bone marrow transplantation demonstrates the intrinsic role of colonic ANGPTL4 in regulating leukocyte infiltration during DSS-induced inflammation. Using immortalized human colon epithelial cells, we revealed that the ANGPTL4-mediated upregulation of tristetraprolin expression operates through CREB and NF-κB transcription factors, which in turn, regulates the stability of chemokines. Together, our findings suggest that ANGPTL4 protects against acute colonic inflammation and that its absence exacerbates the severity of inflammation. Our findings emphasize the importance of ANGPTL4 as a novel target for therapy in regulating and attenuating inflammation.

show abstract

Section: Resultsmentioning

confidence: 95%

Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin

Phua

Sng

Tan

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Tristetraprolin (TTP, also known as Zfp36) is one of the most widely studied RNA binding proteins. It was identified as a regulator involved in the turnover of mRNAs of cytokines, such as, TNF-α [9], IL-2 and IL-17 [10], [11], in an ARE dependent manner. On the contrary, Hu antigen R (HuR ) and Nuclear factor 90 (NF90) are also RNA-binding proteins which bind to IL-2 3′UTR but increase its mRNA stability [12], [13].…”

Section: Introductionmentioning

confidence: 99%

MCPIP1 Down-Regulates IL-2 Expression through an ARE-Independent Pathway

Cao

Liu

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

IL-2 plays a key role in the survival and proliferation of immune cells, especially T lymphocytes. Its expression is precisely regulated at transcriptional and posttranscriptional level. IL-2 is known to be regulated by RNA binding proteins, such as tristetraprolin (TTP), via an AU-rich element (ARE) in the 3′-untranslated region (3′UTR) to influence the stability of mRNA. MCPIP1, identified as a novel RNase, can degrade IL-6, IL-12 and TNF-α mRNA by an ARE-independent pathway in the activation of macrophages. Here, we reported that MCPIP1 was induced in the activation of T lymphocytes and negatively regulated IL-2 gene expression in both mouse and human primary T lymphocytes through destabilizing its mRNA. A set of Luciferase reporter assay demonstrated that a non-ARE conserved element in IL-2 3′UTR, which formed a stem-loop structure, responded to MCPIP1 activity.RNA immunoprecipitation and Biotin pulldown experiments further suggested that MCPIP1 could modestly bind to IL-2 mRNA. Taken together, these data demonstrate that MCPIP1 down-regulates IL-2 via an ARE-independent pathway.

show abstract

“…Tristetraprolin (TTP) is a well-characterized molecule with tandem Cys-Cys-Cys-His (CCCH)-type RNA-binding zinc finger motifs that regulates several cytokines, chemokines, inducible NO synthase, and cyclooxygenase-2 through the AU-rich elementdependent degradation of mRNAs (2,(5)(6)(7)(8)(9). Another example of the CCCH type of RNA binding protein is Roquin, which controls follicular helper T cell differentiation through the repression of the inducible T cell costimulator and Ox40 via 39 untranslated region (UTR) (10)(11)(12).…”

mentioning

confidence: 99%

Posttranscriptional Modulation of Cytokine Production in T Cells for the Regulation of Excessive Inflammation by TFL

Minagawa

Wakahashi

Kawano

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Posttranscriptional machinery regulates inflammation and is associated with autoimmunity as well as tumorigenesis in collaboration with transcription factors. We previously identified the tumor suppressor gene transformed follicular lymphoma (TFL) on 6q25 in a patient with follicular lymphoma, which transformed into diffuse large B cell lymphoma. TFL families have a common RNase domain that governs macrophage-mediated inflammation. In human peripheral blood, TFL is dominantly expressed at the glycine- and tryptophan-rich cytoplasmic processing bodies of T lymphocytes, and it is persistently upregulated in activated T cells. To address its physiological role, we established TFL−/− mice in which TFL−/− lymphocytes proliferated more rapidly than TFL+/+ upon stimulation with inappropriate cytokine secretion, including IL-2, IL-6, and IL-10. Moreover, TFL inhibited the synthesis of cytokines such as IL-2, IL-6, IL-10, TNF-α, and IL-17a by 3′ untranslated region RNA degradation. Experimental autoimmune encephalitis induced in TFL−/− mice demonstrated persistent severe paralysis. CNS-infiltrated CD4+ T cells in TFL−/− mice contained a higher proportion of Th17 cells than did those in TFL+/+ mice during the resolution phase, and IL-17a mRNA levels were markedly increased in TFL−/− cells. These results suggest that TFL may play an important role in attenuating local inflammation by suppressing the infiltration of Th17 cells in the CNS during the resolution phase of experimental autoimmune encephalitis. TFL is a novel gradual and persistent posttranscriptional regulator, and the TFL-driven attenuation of excessive inflammation could contribute to recovery from T cell–mediated autoimmune diseases.

show abstract

Tristetraprolin down‐regulates IL‐17 through mRNA destabilization

Cited by 54 publications

References 22 publications

Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin

Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin

MCPIP1 Down-Regulates IL-2 Expression through an ARE-Independent Pathway

Posttranscriptional Modulation of Cytokine Production in T Cells for the Regulation of Excessive Inflammation by TFL

Contact Info

Product

Resources

About