• Natural Product Sciences
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• v.23 no.1
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• pp.1-4
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• 2017

Sinensetin, a pentamethoxyflavone, is known to exert various pharmacological activities including anti-angiogenesis, anti-diabetic and anti-inflammatory activities. However, its effects on the human mast cell - 1 (HMC-1) mediated inflammatory mechanism remain unknown. To explore the mediator and cellular inflammatory response of sinensetin, we examined its influence on phorbol 12-myristate 13-acetate (PMA) plus A23187 induced inflammatory mediator production in a human mast cell line. In this study, interleukin (IL)-6 production was measured using the enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Sinensetin inhibited PMA plus A23187 induced IL-6 production in a dose-dependent manner as well as IL-4, IL-5 and IL-8 mRNA expression. Furthermore, sinensetin inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation, suggesting that sinensetin inhibits the production of inflammatory mediators by blocking STAT3 phosphorylation. Moreover, sinensetin was found to inhibit nuclear factor kappa B activation. These findings suggest that sinensetin may be involved in the regulation of mast cell-mediated inflammatory responses.

• BMB Reports
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• v.34 no.5
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• pp.484-488
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• 2001

STATs are proteins with a dual function: signal transducers in the cytoplasm and transcriptional activators in the nucleus. Among the six known major STATs (STAT1-6), STAT3 has been implicated in the widest range of signaling pathways that regulate cell growth and differentiation. As a part of our on-going investigation on the pleiotropic functions of STAT proteins, we examined the role of STAT3 as a molecular adaptor that links diverse cell growth signaling pathways. We observed that STAT3 can be specifically activated by multiple cytokines, such as IL-3, in transformed fibroblasts and IL-4 or IFN-$\gamma$ in primary immune cells, respectively. The selective activation of STAT3 in H-ras-transformed NIH3T3 cells is associated with an increased expression of phosphoserioe STAT3 in these cells, compared to the parental cells. Notably phosphoresine-STAT3 interacts with oncogenic ras, shown by immunoprecipitation and Western blots. The results suggest the role of STAT3 in rasinduced cellular transformation as a molecular adaptor linking the Jak/STAT and Ras/MAPK pathways. In primary immune cells, IL-4 and IFN-$\gamma$ each induced (in addition to the characteristic STAT6 and STAT1 homodimers) the formation of STAT3-containing complexes that bind to GAS probes, which correspond to the $Fe{\varepsilon}$ Rll and $Fe{\gamma}$ RI promoter sequences, respectively. Since IL-4 and IFN-$\gamma$ are known to counter-regulate the expression of these genes, the ability of STAT3 to form heterodimeric complexes with STAT6 or STAT1 implies its role in the fine-tuned control of genes that are regulated by IL-4 and IFN-$\gamma$.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.7
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• pp.938-943
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• 2002

This study was perfonned to detect polymorphisms of the two candidate genes, bovine BTN (Butyrophilin) and ST AT5a (Signal Transducers and Activators of Transcription) gene using 98 Holstein bulls' frozen semen, and to offer the basic information for QTL (Quantitative Trait Loci) analysis. Each BTN PCR product was digested with endonuclease restriction enzyme. The digested fragments of four BTN PCR products were observed as follows: 316,280, and 162 bp in BTN1, 568, 305 and 263 bp in BTN2, 576, 332, and 244 bp in BTN3, and 573, 291, and 282 bp in BTN4, respectively. The gene frequencies of A and B allele in four BTN loci were as follows: 0.8980 and 0.1020 in BTN1, 0.5510 and 0.4490 in BTN2, 0.8163 and 0.1837 in BTN3, and 0.8875 and 0.1122 in BTN4, respectively. And three genotypes (homotypel, heterotype, and homotype2) for STAT5a were observed by SSCP (single stranded conformational polymorphism) method and the genotype frequencies are 78.57%, 19.39%, and 2.04%, respectively. The PlC (Polymorphism Information Content) value and heterozygosity of four BTN loci were as follows: 0.1695 and 0.1870 in BTN1, 0.3713 and 0.4927 in BTN2, 0.2549 and 0.2999 in BTN3, and 0.1794 and 0.1992 in BTN4, respectively. Comparing with the reported data, PlC value of BTN2 might have the possibility to be useful marker. Other BTN loci indicated skewed allele distribution.

• Journal of Life Science
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• v.21 no.1
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• pp.141-145
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• 2011

Actinomycin D is a natural antibiotic that is used in anti-cancer chemotherapy and is known as a transcription inhibitor. Interestingly, actinomycin D induces phosphorylation of signal transducers and activators of transcription 3 (STAT3) in renal cancer Caki cells. In this study, we examined the molecular mechanism of actinomycin D-induced STAT3 phosphorylation. Treatment with actinomycin D induced phosphorylation of STAT3 (Tyr705) in a dose- and time-dependent manner. However, actinomycin D did not induce phosphorylation of STAT3 (Ser727), STAT1 (Tyr701) and STAT1 (Ser727). Moreover, actinomycin D-induced STAT3 phosphorylation was caused by decreased protein and mRNA levels of SOCS3, but not by JAK2 and SHP-1. In addition, other transcription inhibitor (5,6-dichloro-1-b-D-ribofuranosyl benzimidazole; DRB) also induced phosphorylation of STAT3 (Tyr705). Taken together, the present study demonstrates that transcriptional inhibitors (actinomycin D and DRB) induce phosphorylation of STAT3 (Tyr705) in Caki cells by down-regulation of SOCS3.

• Genomics & Informatics
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• v.2 no.3
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• pp.126-130
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• 2004

T helper-type 2 cytokines, such as IL-4 and IL-13, may play a central role in allergic diseases. The protein known as signal transducers and activators of transcription 6 (STAT6) is a key transcription factor involved in both IL-4- and -13-mediated biological responses. Two polymorphisms of the STAT 6 gene (exon 1 and G2964A variant) have been found. We investigated whether these STAT6 gene polymorph isms were associated with allergic rhinitis. Blood samples for genetic analysis were obtained from 285 individuals with allergic rhinitis and from 271 healthy subjects without atopic disease. The G2964A variant of the STAT6 gene was genotyped using PCR-RFLP analysis. The GT repeat polymorphism in exon 1 of the STAT6 gene was genotyped by fragment analysis. There was no association between the 2964A variant and GT repeat polymorphism in exon 1 of the STAT6 and allergic rhinitis in a Korean population (both p > 0.05). Our results suggest that a combination of STAT6 gene polymorphisms is not a useful marker for predicting allergic rhinitis.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.2
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• pp.165-169
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• 2005

This study was performed to offer effective basic data for selection and improvement of Korean dairy cattle through identifying distributional properties among candidate genes (bovine butyrophilin, signal transducers and activators of transcription 5a, and prolactin hormone). In this study, polymorphisms of candidate genes were identified and the relationships between loci and production traits of each gene were analyzed using frozen semen of Holstein bulls (19 proven and 77 candidates). In butyrophilin (BTN) locus, polymorphisms information contents (PIC) value of BTN2 (0.372) was higher than those of others (BTN1; 0.155, BTN3; 0.254, BTN4; 0.169). As a result of analysis of genotyping STAT5a, using single stranded conformational polymorphism (SSCP) method and microsatellite locus, PIC values were 0.189 and 0.457, respectively. And PIC value of prolactin hormone gene was 0.176. In the relationships between genotypes and production traits, BTN3 was associated with 305-day production traits (p<0.05). PTAs for B allele were such as 110.43, 88.28 and 75.25 in BTN1, 3, 4 and these values were higher than those of A allele, but in the case of BTN2, A allele with 154.19 was higher than that of B allele. The results obtained from using candidate genes may be used as an useful index for the genetic improvement of dairy cattle population in Korea, and further studies are needed.

• Journal of Marine Life Science
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• v.3 no.2
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• pp.45-50
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• 2018

Rock bream iridovirus (RBIV) is a megalocytivirus widely infected in various fish species in Korea, causing symptoms of acute inflammation and enlargement of spleen. In our previous study, RBIV induced the initial upregulation but later down-regulation of proinflammatory cytokines and IFN1 gene expression. Signal transducers and activators of transcriptions (STAT) are transcription factors involved in the regulation of immune genes including IFNs. This study was conducted to analyse the expression of STAT2. The expressional study of STAT2 gene was performed in head kidney and spleen upon RBIV infection and immune stimulants like LPS or poly I:C in vitro. Consequently, STAT2 gene expression pattern was different in head kidney and spleen as it was significantly up-regulated by LPS from 4 h to 8 h but down-regulated at 24 h while up-regulated by poly I:C at 8 h in head kidney while, in spleen, STAT2 gene expression was down regulated by LPS but significantly up-regulated by poly I:C. Upon RBIV stimulation, STAT2 gene expression was significantly down-regulated by high dose RBIV at 4 h but up-regulated at 8 h and 24 h in head kidney. In spleen cells, it was up-regulated by medium dose RBIV at 4 h and by high dose RBIV at 4 h and 8 h but down regulated later then. In vivo, STAT2 gene expression was not significantly affected by RBIV infection while significant up-regulated by vaccination at day 7 post-vaccination, indicating STAT2 gene can be involved in adaptive immune response in rock bream.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3117-3120
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• 2015

Objective: Interferon-${\gamma}$ (IFN-${\gamma}$) and signal transducers and activators of transcription (STATs) each play an important role in carcinogenesis associated with viral infection. Cervical cancer is almost invariably associated with infection by human papillomavirus (HPV), and previous studies suggested that dysregulation of the signal pathway involved in IFN-${\gamma}$ and STATs is associated. Our objective was to evaluate the association of SNPs in STAT2, STAT3, and IFN-${\gamma}$ with cervical cancer susceptibility in Chinese Han women in Hunan province. Materials and Methods: Genomic DNA was extracted from peripheral blood samples of 234 cervical cancer patients and 216 healthy female controls. STAT2 and STAT3 genotyping was performed using polymerase chain reaction-restriction enzyme (PCR-RE) analysis. IFN-${\gamma}$ genotyping was detected by PCR-amplification of specific allele (PASA). Results: For STAT2 rs2066807 polymorphisms, there was no significant difference of genotype distribution (P=0.827) and allele frequencies (P=0.830, OR=1.09, 95% CI: 0.51-2.31) between cases and controls. For STAT3 rs957970 polymorphisms, there was no significant difference of genotype distribution (P=0.455) and allele frequencies (P=0.560, OR=0.92, 95% CI: 0.71-1.20) between cases and controls. For IFN-${\gamma}$ +874A/T polymorphisms, there was no significant difference of genotype distribution (P=0.652) and allele frequencies (P=0.527, OR=1.12, 95% CI: 0.79-1.59) between cases and controls. Conclusion: These results suggest that polymorphisms in STAT2, STAT3 and IFN-${\gamma}$ genes are not likely to be strong predictors of cervical cancer in Han women in southern China.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.238-244
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• 2015

Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the inflammatory chemokines that controls the movement of monocytes, monocyte-derived dendritic cells, and natural killer cells. Serum and skin MDC/CCL22 levels are elevated in atopic dermatitis, which suggests that the chemokines produced from keratinocytes are responsible for attracting inflammatory lymphocytes to the skin. A major signaling pathway in the interferon-${\gamma}$ (IFN-${\gamma}$)-stimulated inflammation response involves the signal transducers and activators of transcription 1 (STAT1). In the present study, we investigated the anti-inflammatory effect of dieckol and its possible action mechanisms in the category of skin inflammation including atopic dermatitis. Dieckol inhibited MDC/CCL22 production induced by IFN-${\gamma}$ (10 ng/mL) in a dose dependent manner. Dieckol (5 and $10{\mu}M$) suppressed the phosphorylation and the nuclear translocation of STAT1. These results suggest that dieckol exhibits anti-inflammatory effect via the down-regulation of STAT1 activation.

• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.2
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• pp.17-32
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• 2013

Objectives: The purpose of this study was to investigate whether Lonicera japonica(LJ) could inhibit LPS-induced type I IFN production. Methods: To evaluate inhibitory effect of LJ on type I IFN, we examined type I IFN, IRF-1, 7 and IL-10 production on LPS-induced macrophages using real time RT-PCR. Next, we observed the interaction of type I IFN, IRF-1, 7 and IL-10 using IL-10 neutralizing antibody. Finally we examined the activation of STAT-1, 3 using western blot. Results: LJ inhibited Type I IFN expression of mRNA and increased IL-10 expression of mRNA. Also LJ inhibited the level of IRF-1, 7 mRNA and the nuclear translocation of IRF-3. Further more, LJ reduced the activation of STAT-1, 3 which are involved in continuous secretion of immune cytokines. Blockade of IL-10 action caused a significant reduction of type I IFN and IRF-1, 7 than LPS-induced LJ pretreatment. Conclusions: LJ inhibits LPS-induced production of type I IFN by IL-10. This study may provide a clinical basis for anti-inflammatory properties of LJ.