Humans ; Liposarcoma/surgery* ; Retroperitoneal Neoplasms/pathology* ; STAT6 Transcription Factor

OBJECTIVE: Recent molecular and genetic investigations have suggested that the current nosology for major psychiatric disorders, based on the "two-entities-principal" is not accurate with respect to clinical observations; patient groups that do not fit to the current operative diagnostic boundaries are readily identified. We aimed to perform an investigation of the signal transducer and activator of transcription 6 (STAT6) gene (located on 12q13), which has an important role in the apoptotic cascade, with patients suffering from periodic psychosis. METHODS: Genetic association study has been employed for the current work. Investigated six tag-SNPs were chosen from Hapmap database. RESULTS: Among six tag-SNPs, one marker (rs10783813), located in the STAT6 gene, showed modest association (p<0.05), although no marker or haplotype block showed association after Bonferroni's correction. CONCLUSION: Future studies will reveal the etiological role of STAT6, and of other genes of the apoptotic cascade, in major psychiatric disorders.
Genetic Association Studies ; Haplotypes ; HapMap Project ; Humans ; Psychotic Disorders* ; STAT6 Transcription Factor*

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.
Animals ; Cell Line ; Dermatitis, Atopic ; Hypersensitivity ; Interleukin-4* ; Mice ; Phenotype ; Phosphorylation ; STAT6 Transcription Factor

BACKGROUND: We reported that level of lipopolysaccharide (LPS) exposure determined the type of airway inflammation in a murine model of asthma. OBJECTIVE: The purpose of this study is to evaluated the role of IL-13 in low dose LPS induced murine model of asthma using IL-13 and signal transducer and activator of transcription 6 (STAT6) deficient mice. METHODS: Mice were sensitized with an intranasal application of LPS-depleted ovalbumin (OA) and different doses of LPS (0.1 and 10 µg), and then challenged intranasally with OA alone. The phenotype changes between wild type (WT) and IL-13-/- mice and between WT and STAT6-/- mice were evaluated. RESULTS: We confirmed again that low and high dose LPS resulted in different phenotypes of murine asthma. In the present study, we observed that phenotypes of murine asthma induced by low dose LPS were abolished in the homozygous null mutation of the IL-13 and STAT6 gene. However, those changes were not shown in mice sensitized OA plus high dose LPS. CONCLUSION: IL-13 plays an important role in low dose LPS induced murine model of asthma. Our results provided a new insight in understanding of the potential role of IL-13 in innate immunity in human allergic asthma.
Animals ; Asthma ; Humans ; Immunity, Innate ; Inflammation ; Interleukin-13 ; Mice ; Models, Animal ; Ovalbumin ; Phenotype ; STAT6 Transcription Factor

Animals ; Humans ; STAT6 Transcription Factor ; chemistry ; genetics ; metabolism ; Structure-Activity Relationship

To study the effect of anemoside B4 on rats with chronic obstructive pulmonary disease (COPD).Seventy-two SD male rats were randomly divided into blank group and model group.The method of exposure to cigarette smoke and combined with lipopolysaccharide (LPS) was used to replicate the rat model of COPD.After the model was maintained for 5 weeks,the rats were randomly divided into model group,dexamethasone group (0.81 mg·kg~(-1)) and anemoside B4 low,medium and high (2,4,8 mg·kg~(-1)) dose groups,a group of 12 animals were administered,and then the administration was started.The administration was maintained until the28th day,and the pulmonary function parameters of rats were measured by an animal pulmonary function instrument.After testing the rat lung function parameters,immediately draw rat alveolar lavage fluid (BALF),and use high-throughput protein chip technology to determined the expression levels of inflammatory cytokines in rat BALF.HE staining was used to observe the general pathological changes of rat lung and tracheal tissue.Masson staining was used to observe the collagen deposition in rat lung tissue.Real-time q PCR method was used to determine the mRNA expression level of related genes in rat lung tissue.Western blot method was used to determine the expression levels of related proteins in rat lung tissues.According to the findings,compared with the model group,the dexamethasone group and the anemoside B4 drug groups had different degrees of increase in the lung function parameters of rats (P<0.01,P<0.05),improved the expression level of inflammatory cytokines in the BALF of rats to varying degrees (P<0.01,P<0.05),and improved the pathological structure of rat lung tissue to varying degrees.Relative mRNA expressions of matrix metalloproteinase 2 (MMP-2),matrix metalloproteinase 12 (MMP-12),matrix metalloproteinase inhibitor 1 (TIMP-1),interleukin-6 (IL-6),and transforming growth factor-β1 (TGF-β1) were significantly reduced (P<0.01);whereas relative mRNA expressions of matrix metalloproteinase 9(MMP-9) and matrix metalloproteinase inhibitor 2 (TIMP-2) were increased significantly (P<0.01).The mRNA and protein expression levels of T-box transcription factor (T-bet),interleukin-12 (IL-12) and signal transducer and activator of transcription 4(STAT4) reduced to varying degrees (P<0.01,P<0.05).The mRNA of transcription factor GATA3 (binding protein-3),interleukin-4 (IL-4) and signal transducer and activator of transcription 6 (STAT6) in rat lung tissues and the protein expression levels of IL-4 and STAT6 were increased to varying degrees (P<0.01,P<0.05).In conclusion,anemoside B4 has a certain protective effect on COPD rats caused by cigarette smoke exposure and combined with LPS.The mechanism of action may be related to the regulation of IL-12/STAT4 and IL-4/STAT6 signaling pathways.
Animals ; Interleukin-12 ; Interleukin-4 ; Lung/metabolism* ; Male ; Matrix Metalloproteinase 2 ; Pulmonary Disease, Chronic Obstructive/genetics* ; Rats ; STAT4 Transcription Factor/metabolism* ; STAT6 Transcription Factor/metabolism* ; Saponins

Obesity results in an inflammatory microenvironment in adipose tissue, leading to the deterioration of tissue protective mechanisms. Although recent studies suggested the importance of type 2 immunity in an anti-inflammatory microenvironment in adipose tissue, the regulatory effects of T helper 2 (Th2) cytokines on systemic metabolic regulation are not fully understood. Recently, we identified the roles of the Th2 cytokine (interleukin 4 [IL-4] and IL-13)-induced adipokine, growth differentiation factor 15 (GDF15), in adipose tissue in regulating systemic glucose metabolism via signal transducer and activator of transcription 6 (STAT6) activation. Moreover, we showed that mitochondrial oxidative phosphorylation is required to maintain these macrophage-regulating autocrine and paracrine signaling pathways via Th2 cytokine-induced secretion of GDF15. In this review, we discuss how the type 2 immune response and Th2 cytokines regulate metabolism in adipose tissue. Specifically, we review the systemic regulatory roles of Th2 cytokines in metabolic disease and the role of mitochondria in maintenance of type 2 responses in adipose tissue homeostasis.
Adipokines ; Adipose Tissue ; Cytokines ; Glucose ; Growth Differentiation Factor 15 ; Homeostasis ; Metabolic Diseases ; Metabolism ; Mitochondria ; Obesity ; Oxidative Phosphorylation ; Paracrine Communication ; STAT6 Transcription Factor

Toxoplasma gondii provokes rapid and sustained nuclear translocation of the signal transducer and activator of transcription 6 (STAT6) in HeLa cells. We observed activation of STAT6 as early as 2 hr after infection with T. gondii by the nuclear translocation of fluorescence expressed from exogenously transfected pDsRed2-STAT6 plasmid and by the detection of phosphotyrosine-STAT6 in Western blot. STAT6 activation occurred only by infection with live tachyzoites but not by co-culture with killed tachyzoites or soluble T. gondii extracts. STAT6 phosphorylation was inhibited by small interfering RNA of STAT6 (siSTAT6). In view of the fact that STAT6 is a central mediator of IL-4 induced gene expression, activation of STAT6 by T. gondii infection resembles that infected host cells has been stimulated by IL-4 treatment. STAT1 was affected to increase the transcription and expression by the treatment of siSTAT6. STAT6 activation was not affected by any excess SOCS's whereas that with IL-4 was inhibited by SOCS-1 and SOCS-3. T. gondii infection induced Eotaxin-3 gene expression which was reduced by IFN-gamma. These results demonstrate that T. gondii exploits host STAT6 to take away various harmful reactions by IFN-gamma. This shows, for the first time, IL-4-like action by T. gondii infection modulates microbicidal action by IFN-gamma in infected cells.
Active Transport, Cell Nucleus ; Animals ; Chemokines, CC/biosynthesis ; Hela Cells ; Humans ; Interleukin-4/*immunology ; Mice ; Mice, Inbred BALB C ; STAT6 Transcription Factor/*immunology/*metabolism ; Toxoplasma/*immunology

AIMTo study the effect of achyranthes bidentata polysaccharides(ABPS) on the expression of signal transducer and activator of transcription 6 and its mRNA in bronchus of a rat model of asthma.

METHODSThirty male SD rats were randomly divided into three groups: the control group, asthma group and ABPS group. The total cell numbers, eosinophils (EOS) numbers and differentiated cell numbers in bronchoalveolar lavage fluid (BALF) were counted by different count fluids. The concentrations of IL-4 in serum and BALF were measured by sandwich ELISA. The protein expressions of STAT6 were detected by immunohistochemistry techniques. The mRNA expressions of STAT6 were detected by hybridization in situ.

RESULTS(1) The total cell numbers in BALF, the absolute numbers of EOS, the ratios of eosinophils to the total cell numbers (EOS%) of asthma group were all significantly higher than those of the control group (P < 0.01). The total cell numbers in BALF, the absolute numbers of EOS and EOS% of ABPS group were all significantly lower than those of asthma group (P < 0.01). (2) The concentrations of IL-4 in BALF and serum of asthma group were significantly higher than those of control group (P < 0.01), while the concentrations of IL-4 in BALF and serum of ABPS group were significantly lower than those of asthma group. (3) Immunohistochemistry showed that the protein content of STAT6 around the bronchus of asthma group was significantly higher than that of the control group (P < 0.01), while that of ABPS group was significantly lower than that of asthma group , the epithelial cells were the chief expression cells; hybridization in situ showed that the mRNA expression of STAT6 around the bronchus of asthma group was significantly higher than that of the control group (P < 0.01), while that of ABPS group was significantly lower than that of asthma group , the epithelial cells were the chief expression cells.

CONCLUSIONSTAT6 protein and STAT6 mRNA were found strongly expressed in rat asthma model, the epithelial cells were the chief expression cells. ABPS had an inhibitory effect on airway inflammation cells infiltration such as EOS, it significantly depressed STAT6 and its mRNA expression, thus reduced the synthesis of IL-4 might be key in modulating mechanism of asthma.

Achyranthes ; Animals ; Asthma ; metabolism ; Eosinophils ; metabolism ; Interleukin-4 ; metabolism ; Male ; Polysaccharides ; pharmacology ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; STAT6 Transcription Factor ; metabolism ; Signal Transduction

OBJECTIVE: To study the distribution and expression of STAT6 and to examine the suggested roles of STAT6 in the pathogenesis of eosinophil infiltration in nasal polyps and to evaluate the role of STAT6 in the pathogenesis of nasal polyps. METHOD: All selected cases met the enrollment criteria. Thirty samples of nasal polyps were obtained from patients undergoing nasal polypectomy, and 10 samples of inferior turbinate tissues were from patients undergoing nasal septal reconstruction. STAT6 in nasal polyp tissues from 30 nasal polyposis patients and 10 samples of inferior turbinate tissues were detected with immunohistochemistry (SP) method. SPSS13.0 system was used to perform the statistical analysis. RESULT: The positive expression of STAT6 was significantly higher in epithelium of nasal polyps than that of the control. The number of eosinophils was significantly higher in epithelium of nasal polyps than that of the control. The difference between these two groups was statistically significant (P<0.05). STAT6 positive cell were localized on epithelium, gland cells and on inflammatory cell of nasal polyps. STAT6 expression was positively correlated with the recruitment of eosinophils in nasal polyps. CONCLUSION The high expression of STAT6 protein and the suggested roles of STAT6 in the recruitment of eosinophils in nasal polyps may contribute to the initiation and progression of nasal polyps.
Adolescent ; Adult ; Aged ; Eosinophils ; pathology ; Female ; Humans ; Inflammation ; Male ; Middle Aged ; Nasal Polyps ; metabolism ; pathology ; STAT6 Transcription Factor ; metabolism ; Young Adult