• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.592-597
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• 2010

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disease which is characterized by high serum IgE levels, eczema, and recurrent infections. Herein we present the case of a patient with HIES associated with STAT3 gene ($stat3$) mutation. A 16 year-old girl was admitted to our hospital due to hemoptysis caused by pneumonia with bronchiectasis. She had a history of recurrent skin and respiratory tract infections, such as pneumonia caused by MRSA (methicillin-resistant $Staphylococcus$ $aureus$) and $Pseudomonas$ $aeruginosa$. On physical examination, a broad round shaped nose, oral thrush, and chronic eczematous skin rash over her whole body were found. Laboratory data showed an elevated eosinophil count ($750/{\mu}L$) and total IgE level (5,001 U/mL). The patient's National Institutes of Health (NIH) score for HIES was 44. Direct sequencing of the STAT3 gene revealed that the patient was heterozygous for a missense mutation in the DNA binding domain of the STAT3 protein (c.1144C>T, p. Arg382Trp). HIES should be suspected in patients with recurrent infections and can be confirmed by clinical scoring and genetic analysis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4823-4827
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• 2013

Objective: To study the mechanism of effects of AZD1480 on the SKOV3 ovarian cancer cell line. Methods: The MTT method was used to assess cellular proliferation, flow cytometry for cellular apoptosis, the scratch test to determine migration, transwell chamber assays to detect cellular invasion, plate clone experiments to detect the clone forming ability and Western blotting to determine p-STAT3 protein levels. Results: The proliferation rate, migration ability, invasiveness and the clone forming ability of SKOV3 cells were reduced after treatment with AZD1480, while apoptosis rate and chemotherapeutic susceptibility were increased. After treatment with AZD1480 plus cisplatin, the apoptosis rate increased significantly while the expression level of p-STAT3 protein was decreased. Conclusion: AZD1480 can inhibit the proliferation, invasion, metastasis and clone formation of SKOV3 cells, induce cellulsar apoptosis, increase the chemotherapeutic sensitivity and reduce the expression level of p-STAT3 protein.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.100-109
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• 2015

Controlling balance between T-helper type 1 (Th1) and T-helper type 2 (Th2) plays a pivotal role in maintaining the biological rhythm of Th1/Th2 and circumventing diseases caused by Th1/Th2 imbalance. Interleukin 4 (IL-4) is a Th2-type cytokine and often associated with hypersensitivity-related diseases such as atopic dermatitis and allergies when overexpressed. In this study, we have tried to elucidate the function of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) as an essential modulator of Th1/Th2 balance. EC-18 has showed an inhibitory effect on the production of IL-4 in a dose-dependent manner. RT-PCR analysis has proved EC-18 affect the transcription of IL-4. By analyzing the phosphorylation status of Signal transducer and activator of transcription 6 (STAT6), which is a transcriptional activator of IL-4 expression, we discovered that EC-18 induced the decrease of STAT6 activity in several stimulated cell lines, which was also showed in STAT6 reporter analysis. Co-treatment of EC-18 significantly weakened atopy-like phenotypes in mice treated with an allergen. Collectively, our results suggest that EC-18 is a potent Th2 modulating factor by regulating the transcription of IL-4 via STAT6 modulation, and could be developed for immune-modulatory therapeutics.

• The Korea Journal of Herbology
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• v.27 no.4
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• pp.9-16
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• 2012

Objective : Canavalia gladiata DC semen (CGS) have been used to improve hematopoietic activity. In the current study, we investigated whether CGS regulate hemato-potentiating function using hematopoietic stem cells (HSCs) as a testing system. Methods : HSCs isolated from femur in mice with leukopenia and thrombocytopenia induced induced by CTX. Then, Real-time PCR was performed to measure the mRNA expression and hematopoietic related gene (EPO, IL-3, SCF, c-kit, GM-CSF), the phoaphorylation of GATA-1 and STAT-5a/b were observed by ELISA method, and the number of granulocyte erythrocyte monocyte macrophage colony-forming units (CFU-GEMM) and erythroid burst forming units (BFU-E), semisolid clonogenic assay was performed. Result : When HSCs were treated with CGS, the expression of hematopoietic related genes (EPO, IL-3, SCF, c-kit, and GM-CSF) were significantly increased at the levels of mRNA as well as production in HSCs. Additionally, CGS enhanced phosphorylation of STAT-1 and signal transducer and activator of transcription-5a/b (STAT-5a/b) in HSCs. Furthermore, CGS significantly enhanced the growth rate of granulocyte erythrocyte monocyte macrophage colony-forming units (CFU-GEMM) and erythroid burst forming units (BFU-E) in vitro. Conclusion : These result suggest that CGS has hematopoietic enhancement via hematopoietic cytokine-mediated GATA-1/STAT-5a/b pathway.

• Mycobiology
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• v.43 no.3
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• pp.319-326
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• 2015

Fomes fomentarius is a fungus of the Polyporaceae family and is used in traditional oriental therapies. Although the anti-inflammatory activities of this species have been previously reported, the identity of the bioactive compounds responsible for this activity remains unknown. Here, we investigated whether methyl 9-oxo-(10E,12E)-octadecadienoate (FF-8) purified from F. fomentarius exerts anti-inflammatory activity in murine macrophages stimulated with lipopolysaccharide (LPS). FF-8 suppressed secretion of nitric oxide (NO) and prostaglandin $E_2$ through downregulation of inducible NO synthase and cyclooxygenase-2 expression induced by LPS. In addition, pretreatment of cells with FF-8 led to a reduction in levels of secreted inflammatory cytokines such as tumor necrosis factor-${\alpha}$ and interleukin-6 in macrophages stimulated with LPS. Conversely, FF-8 did not affect nuclear factor ${\kappa}B$, p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase pathways. Instead, FF-8 specifically interfered with signal transducer and activator of transcription 3 (STAT3) phosphorylation induced by LPS. Collectively, this study demonstrated that FF-8 purified from F. fomentarius suppresses inflammatory responses in macrophages stimulated with LPS by inhibiting STAT3 activation. Further studies will be required to elucidate the anti-inflammatory effect of FF-8 in vivo.

• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3661-3664
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• 2014

• IMMUNE NETWORK
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• v.21 no.5
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• pp.33.1-33.19
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• 2021

IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8⁺ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8⁺ T cells and features of IL-1R⁺ CD8⁺ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8⁺ T cells. Further, IL-1β enhances the effector function of CD8⁺ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8⁺ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8⁺ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8⁺ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

• Korean Journal of Veterinary Service
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• v.35 no.4
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• pp.269-273
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• 2012

A confirmatory serological test, the standard tube agglutination test (STAT) is evaluated for the diagnostic efficiency in brucellosis Korea. A total of 345 bovine samples were collected from regional veterinary branch under national brucellosis monitoring program from January 2010 to June 2012 in Korea. These samples were diagnosed as suspected serum and brucellosis positive by the Rose Bengal test (RBT) and the STAT, respectively. The STAT was compared and evaluated with three serological test such as the indirect-enzyme linked immunosorbent assay (I-ELISA), competitive-enzyme linked immunosorbent assay (C-ELISA) and fluorescence polarisation assay (FPA) prescribed for international trade by OIE. Among the 345 bovine serum samples, 302 (87.5%) were diagnosed as positive in the STAT, while 215 (62.3%), 223 (64.6%) and 194 (56.2%) serum samples were diagnosed as positive for brucellosis in the I-ELISA, C-ELISA and FPA, respectively. The STAT showed quite high positive results as compared with three prescribed tests of OIE. FPA, I-ELISA and C-ELISA have shown 60.6%, 64.9% and 67.2% correlation, respectively as compared to the STAT. However correlations of three prescribed tests ranged high 84.1~97.7%. Especially, correlation between I-ELISA and C-ELISA is quite high, 97.7%. These results suggest that the STAT has shown many false-positive reactions. Therefore, additional serological test, such as ELISAs and FPA, would be necessary to adopt as a confirmatory test in the national surveillance program of bovine brucellosis in Korea.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2151-2157
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• 2016

Scabraside D, a sulfated triterpene glycoside, was extracted from the sea cucumber Holothuria scabra. It shows anti-proliferation in many of cancer cell lines, but the function and mechanisms of action of scabraside D in human cholangiocarcinoma (HuCCA) have not previously determined. In this study, we investigated the activity of scabraside D on HuCCA cell apoptosis, lymphangiogenesis and metastasis in a nude mouse model. Scabraside D induced signs of apoptosis, such as cell shrinkage, nuclear condensation, nuclear fragmentation and DNA fragmentation on TUNEL assays, while effectively decreasing expression of BCl-2 but increasing caspase-3 gene level expression. Immunohistochemistry revealed that scabraside D significantly reduced lymphatic vessel density (LVD). Moreover, scabraside D treatment significantly decreased VEGF-C, MMP-9 and uPA gene expression, which play important roles in the lymphangiogenesis and invasion of cancer cells in metastasis processes. Quantitative real-time PCR showed that scabraside D significantly decreased iNOS and STAT-3 gene expression. This study demonstrated that scabraside D plays a role in activation of HuCCA tumor apoptosis and inhibition of lymphangiogenesis, invasion and metastasis through decreasing BCl-2, MMP-9, uPA and VEGF-C and increasing caspase-3 expression by suppression of iNOS and STAT-3 expression. Therefore, scabraside D could be a promising candidate for cholangiocarcinoma treatment.

• BMB Reports
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• v.50 no.12
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• pp.628-633
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• 2017

Gastrin-releasing peptide (GRP) has been reported to be implicated in the pathogenesis of inflammatory disorders. The migration and proliferation of vascular smooth muscle cells (VSMCs) are key components of vascular inflammation that leads to the development of atherosclerosis. The present study aimed to investigate the molecular effect of GRP on VSMC proliferation and migration. We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase-2 and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the activation of the signal transducer and activator of transcription-3 (STAT3). In addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via STAT3 activation.