The role of TRB3 in mast cells sensitized with monomeric IgE

Kuo, Chuan-Hui; Morohoshi, Kei; Aye, Cho Cho; Garoon, Robert B.; Collins, Andrea; Ono, Santa Jeremy

doi:10.1016/j.yexmp.2012.09.008

Cited by 7 publications

(8 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 In another study, knockdown of TRB3 by siRNA significantly induced the production of TNF-a in RBL-CCR1 cells. 28 These results suggest a feedback relationship between TRB3 and TNF-a.…”

Section: Discussionmentioning

confidence: 83%

Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia

Cheng¹,

Wang³

et al. 2017

Journal of the Formosan Medical Association

View full text Add to dashboard Cite

Background/Purpose: TRB3 (tribbles 3), an apoptosis-regulated gene, increases during endoplasmic reticulum stress. Hypoxia can induce inflammatory mediators and apoptosis in cardiomyocytes. However, the expression of TRB3 in cardiomyocyte apoptosis under hypoxia is not thoroughly known. We investigated the regulation mechanism of TRB3 expression and apoptosis induced by hypoxia in cardiomyocytes. Methods: An in vivo model of acute myocardial infarction (AMI) was applied in adult Wistar rats to induce myocardial hypoxia. Rat neonatal cardiomyocytes were subjected to 2.5% O 2 to induce hypoxia. Results: The expression of TRB3 was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia. Hypoxia significantly enhanced TRB3 protein and mRNA expression. Adding c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA), tumor necrosis factor-a (TNF-a) antibody, and atorvastatin 30 minutes before hypoxia reversed the induction of TRB3 protein. A gel-shift assay showed the DNA-binding activity of growth arrest and DNA damage-inducible gene 153 (GADD153), which increased after hypoxia. Hypoxia increased, whereas the TRB3-mut plasmid, SP600125, and TNF-a antibody abolished the hypoxia-induced TRB3 promoter activity. Hypoxia increased the secretion of TNF-a from cardiomyocytes. Exogenous administration of TNF-a recombinant protein to the cardiomyocytes without hypoxia increased TRB3 protein expression, similar to that observed after hypoxia. Hypoxia-induced cardiomyocyte apoptosis is inhibited by TRB3 siRNA, the TNF-a antibody, and atorvastatin. Atorvastatin reduced the TRB3 expression and cardiomyocyte apoptosis induced by AMI. Hypoxia induces TRB3 through TNF-a, JNK, and the GADD153 pathway. Conclusion: Treatment of atorvastatin inhibits the expression of TRB3 and cardiomyocyte apoptosis induced by AMI and hypoxia.

show abstract

“…27 In another study, knockdown of TRB3 by siRNA significantly induced the production of TNF-a in RBL-CCR1 cells. 28 These results suggest a feedback relationship between TRB3 and TNF-a.…”

Section: Discussionmentioning

confidence: 83%

Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia

Cheng¹,

Wang³

et al. 2017

Journal of the Formosan Medical Association

View full text Add to dashboard Cite

show abstract

“…In the kidney, our studies suggest that TRB3 inhibits inflammatory cytokines and chemokines, as TRB3 inhibits podocyte expression of monocyte chemokine protein 1 (MCP-1) [53]. Kuo and colleagues have similar findings, and knockdown of TRB3 in sensitized mast cells increases expression of IL-6, MCP-1, TNF α , and IL-4, suggesting again that TRB3 may negatively regulate the expression of pro-inflammatory cytokines and chemokines [94]. Early work by Marc Montminy's group demonstrated that TRB3 binds to and masks phosphorylation of Protein Kinase B/AKT at Threonine (Thr) 308 and Serine (Ser) 473 residues, thereby reducing insulin-stimulated glucose output in liver cells [95].…”

Section: Functions Of Trb Isoformsmentioning

confidence: 91%

“…As previously discussed, TRB1 is a novel binding partner of FOXP3, a master regulator of regulatory T cells [74]; thus, it is likely that TRB1 plays a significant role in immune cell function. Furthermore, TRB1 deficiency impairs cytokine gene expression in white adipocytes [50], and TRB1 is involved in cytokine and chemokine expression of mast cells [94] and polarization of M2 macrophages [51]. Helicobacter pylori is a bacterial pathogen that causes stomach inflammation and in gastric epithelial cells TRB3 enhances Toll-like receptor 2 (TLR2)-mediated NF- κ B activation and chemokine induction in response to H. pylori LPS [119].…”

Section: Inflammationmentioning

confidence: 99%

Mammalian Tribbles Homologs at the Crossroads of Endoplasmic Reticulum Stress and Mammalian Target of Rapamycin Pathways

Cunard

2013

Scientifica

View full text Add to dashboard Cite

In 2000, investigators discovered Tribbles, a Drosophila protein that coordinates morphogenesis by inhibiting mitosis. Further work has delineated Xenopus (Xtrb2), Nematode (Nipi-3), and mammalian homologs of Drosophila tribbles, which include TRB1, TRB2, and TRB3. The sequences of tribbles homologs are highly conserved, and despite their protein kinase structure, to date they have not been shown to have kinase activity. TRB family members play a role in the differentiation of macrophages, lymphocytes, muscle cells, adipocytes, and osteoblasts. TRB isoforms also coordinate a number of critical cellular processes including glucose and lipid metabolism, inflammation, cellular stress, survival, apoptosis, and tumorigenesis. TRB family members modulate multiple complex signaling networks including mitogen activated protein kinase cascades, protein kinase B/AKT signaling, mammalian target of rapamycin, and inflammatory pathways. The following review will discuss metazoan homologs of Drosophila tribbles, their structure, expression patterns, and functions. In particular, we will focus on TRB3 function in the kidney in podocytes. This review will also discuss the key signaling pathways with which tribbles proteins interact and provide a rationale for developing novel therapeutics that exploit these interactions to provide better treatment options for both acute and chronic kidney disease.

show abstract

“…The increased BMP signaling by phenamil is thought to be through the induction of tribbles homolog 3 (Trib3) that degrades Smad ubiquitin regulatory factor 1 (Smurf1), a negative regulator of BMP receptor-regulated Smads 13 , 15 , 17 . Moreover, recent studies suggest that Trib3 suppresses the expression of peroxisome proliferator activated receptor gamma (PPARγ), a master regulator of adipogenesis, and serves as a negative regulator of pro-inflammatory cytokines 18 – 22 . Thus, phenamil treatment has high potential to effectively complement the BMP activity to maximize osteogenesis without exogenous application of supraphysiological BMP doses while inhibiting BMP-induced adverse outcomes (i.e.…”

Section: Introductionmentioning

confidence: 99%

Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2

Fan

Pi-Anfruns

Guo

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics.

show abstract

The role of TRB3 in mast cells sensitized with monomeric IgE

Cited by 7 publications

References 46 publications

Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia

Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia

Mammalian Tribbles Homologs at the Crossroads of Endoplasmic Reticulum Stress and Mammalian Target of Rapamycin Pathways

Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2

Contact Info

Product

Resources

About