IL‐13 upregulates GPIIb expression in megakaryocytic cell lines via STAT6

Shi, Xiaoyu; Cai, Wei; Zhou, Ying; Zhang, Xuejun; Xiong, Likuan; Li, Rong; Yu, Xiaobing; Li, Wenlin

doi:10.1002/ar.21144

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…For example, CCL26 is regulated by IL‐4 in a STAT6‐dependent manner in keratinocytes . GPIIb is up‐regulated by IL‐13 via STAT6 in megakaryocytic cell lines . IL‐13 stimulation enhanced promoter activity of the rat RhoA gene through STAT6 .…”

Section: Discussionmentioning

confidence: 99%

Signal transducer and activator of transcription 6 directly regulates human ORMDL3 expression

et al. 2013

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Orosomucoid-like 3 (ORMDL3) has been associated with asthma and a series of autoimmune disorders, and is involved in endoplasmic reticulummediated inflammatory responses. However, its clinical significance and the molecular mechanism underlying its expression are still largely unclear. To elucidate the mechanisms of human ORMDL3 transcriptional regulation, we cloned a 1.5 kb genomic DNA fragment containing the putative promoter region and evaluated its transcriptional activity in a luciferase reporter system by deletion analysis. We identified a 68 bp region that functions as a minimal promoter. Bioinformatics analysis predicted that the À64 to À56 bp region contained a signal transducer and activator of transcription 6 (STAT6) binding site. Electrophoretic mobility shift assay and chromatin immunoprecipitation demonstrated that STAT6 bound to its binding site within the ORMDL3 promoter. STAT6 over-expression or knockdown trans-activated or trans-inhibited, respectively, the ORMDL3 promoter containing the STAT6-binding motif. Treatment with interleukins 4 or 13 increased ORMDL3 promoter activity as well as endogenous ORMDL3 expression. Immunoprecipitation and ChIP/Re-ChIP assays revealed that STAT6 and p300 exist in the same protein complex that binds to the ORMDL3 promoter. Our study confirmed that STAT6 plays important roles in regulating the expression of human ORMDL3 by directly binding to the promoter region, which may shed light on a possible role in various human diseases.Structured digital abstract p300 physically interacts with STAT6 by anti bait coimmunoprecipitation (View Interaction: 1, 2)

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Section: Discussionmentioning

confidence: 99%

Signal transducer and activator of transcription 6 directly regulates human ORMDL3 expression

et al. 2013

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“…Zivancevic-Simonovic et al (15) determined that IL-9 and IL-13 were higher in PTC patients than in healthy controls. All these cytokines (IL-6, IL-9, and IL-13) are known to be able to stimulate platelet production (16,17). Increased platelet generation may lead to occurrence of large thrombocytes (18), hence, to elevated PDW levels.…”

Section: Discussionmentioning

confidence: 99%

Comparison of platelet indices in papillary thyroid carcinoma and microcarcinoma

Güvendi¹,

Kara²,

Binnetoğlu³

et al. 2018

J Turgut Ozal Med Cent

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Aim: Papillary thyroid carcinoma (PTC) is the most common primary thyroid malignancy. It is called papillary thyroid microcarcinoma (PTMC) if the nodule is less than 10 mm in diameter. It has been shown that platelets may play an essential role during chronic inflammation, cancer progression, and metastasis. The aim of this study was to examine the value of platelet indices including platelet count, mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) in PTC. Material and Methods: 26 patients (19 female, 7 male) with PTC diagnosis were included in the study. The patients were divided into two groups: papillary thyroid microcarcinoma (PTMC) and PTC. All patients who were included in the study were examined for complete blood count parameters. Results: There was no significant difference between the groups in terms of age and gender. Leukocyte count, neutrophil count and percentage, lymphocyte count and percentage, platelet count, plateletcrit, and MPV were not statistically different between groups. PDW were significantly higher in patients with PTC than in those with PTMC. Conclusion: Our results show that patients with PTC have higher PDW levels compared to patients with PTMC. Elevated PDW in PTC may be useful in diagnosis of the disease and for better understanding of its pathogenesis.

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“…Since platelets, being cell fragments derived from the precursor megakaryocytes, cannot proliferate in the cell culture system due to a lack of nucleus, there are no cell lines available for the molecular study of platelets. The megakaryocytic cell line (Dami cells) has frequently been used for the study of platelets (Khetawat et al 2000; Shi et al 2010; Lev et al 2011). The goal of the present study was to determine which P450s are expressed in Dami cells with the functional activity for the metabolism of ARA.…”

Section: Introductionmentioning

confidence: 99%

Expression of arachidonic acid-metabolizing cytochrome P450s in human megakaryocytic Dami cells

Jarrar

Shin

Lee

2013

In Vitro Cell.Dev.Biol.-Animal

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Cytochrome P450s (P450s) are involved in the metabolism of arachidonic acid (ARA), and ARA metabolites are associated with various cellular signaling pathways, such as blood hemostasis and inflammation. The present study demonstrates the expression of ARA-metabolizing P450s in the human megakaryocytic Dami cells using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunublotting analysis followed by activity assays using ARA as a substrate. In addition to the previously identified CYP5A1, both protein and mRNAs of CYP1A1, 2U1, and 2J2 bands were detected. Ethoxyresorufin-O-deethylase (EROD) activity was observed in Dami cells, and its activity was significantly decreased after treatment with the P450 inhibitor SKF-525A when compared to the control groups (60% reduction, P < 0.001). CYP1A1 protein expression in Dami cells was induced by 3-methylenecholantheren. This increase in CYP1A1 protein level was correlated with enhanced EROD activity (fourfold increase vs. the control), as well as with increased metabolites, such as 20-hydroxyeicosatrienoic acid (20-HETE), 14, 15-EET (14-,15-epoxyeicosatrienoic acid), and 14, 15-dihydroxyeicosatrienoic acid (14, 15-DHET). The expression of soluble epoxide hydrolase, an enzyme responsible for the synthesis of DHETs from EETs, was confirmed by RT-PCR. Furthermore, 15 ARA metabolites, including 8,9-EET, 14,15-EET, and 20-HETE, were detected by LC-MS/MS in ARA-treated Dami cells, and their levels were decreased with the treatment of the SKF-525A. The present data suggest the possibility that the P450s play a role in the metabolism of ARA and other CYP-related substrates in human megakaryocytes and that P450 expression in megakaryocytic cell lines may predict their existences in platelets with functional activities.

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IL‐13 upregulates GPIIb expression in megakaryocytic cell lines via STAT6

Cited by 4 publications

References 41 publications

Signal transducer and activator of transcription 6 directly regulates human ORMDL3 expression

Signal transducer and activator of transcription 6 directly regulates human ORMDL3 expression

Comparison of platelet indices in papillary thyroid carcinoma and microcarcinoma

Expression of arachidonic acid-metabolizing cytochrome P450s in human megakaryocytic Dami cells

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