-
Jie Tian,
Jie Ma,
Ke Ma,
Bin Ma, Xinyi Tang,
Samuel Essien Baidoo,
Jia Tong,
Jun Yan,
Liwei Lu,
Huaxi Xu,
Shengjun Wang
[show abstract]
[hide abstract]
ABSTRACT: β-Glucans have been shown to function as a potent immunomodulator to stimulate innate and adaptive immune responses, which contributes to their anti-tumor property. However, their mechanisms of action are still elusive. Glucocorticoid-induced TNF receptor ligand (GITRL), a member of the TNF superfamily, binds to its receptor, GITR, on both effector and regulatory T cells, generates a positive co-stimulatory signal implicated in a wide range of T cell functions, which is important for the development of immune responses.
In this study, we found that whole β-glucan particles (WGPs) could activate dendritic cells (DCs) via dectin-1 receptor, and increase the expression of GITRL on DCs in vitro and in vivo. Furthermore, we demonstrated that the increased GITRL on DCs could impair the regulartory T cell (Treg)-mediated suppression and enhance effector T cell proliferation in a GITR/GITRL dependent way. In tumor models, DCs with high levels of GITRL were of great potential to prime cytotoxic T lymphocyte (CTL) responses and down-regulate the suppressive activity of Treg cells, thereby leading to the delayed tumor progression.
These findings suggest that particulate β-glucans can be used as an immunomodulator to stimulate potent T cell-mediated adaptive immunity while down-regulate suppressive immune activity via GITR/GITRL interaction, leading to a more efficient defense mechanism against tumor development.
PLoS ONE 01/2012; 7(10):e46936. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Follicular helper T (Tfh) cells exert an important role in the autoimmune diseases.
Our study aimed to explore the role of Tfh cells in patients with autoimmune thyroid disease (AITD).
Tfh cell is a new subset regulating the antibody production of B cell. Previous studies implicated CD4+CXCR5+ICOShigh or CD4+CXCR5+PD-1high as the markers of circulating Tfh cells. Sixty-five patients with AITD and 30 healthy controls were enrolled in the current study. The percentages of circulating Tfh cells were assessed by flow cytometry. The correlation between the percentages of CD4+CXCR5+ICOShigh T cells and the levels of autoantibodies or hormones was also analyzed. Additionally, polyphasic methods were applied to investigate the status of Tfh cells in thyroid glands of Hashimoto's thyroiditis patients.
Increased percentages of circulating Tfh cells in AITD patients were detected, and a positive correlation between the percentages of circulating Tfh cells and the serum concentrations of anti-TSH receptor-Ab/thyroperoxidase-Ab/thyroglobulin-Ab was confirmed. A positive or modest relationship between the percentages of circulating Tfh cells and serum free T3 or free T4 was revealed in Graves' disease patients. Additionally, follow-up analysis indicated that in some Graves' disease patients the percentage of circulating Tfh cells decreased after treatment. Furthermore, a certain number of CD4+CXCR5+ICOShigh T cells together with enhanced expression of IL-21 and Bcl-6 mRNA were detected in thyroid tissues from Hashimoto's thyroiditis patients.
The current study discovered an increased frequency of Tfh cells in AITD patients, which implies that this cell subset might play an important role in the pathogenesis of AITD.
The Journal of clinical endocrinology and metabolism 12/2011; 97(3):943-50. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Resveratrol, a phytoalexin found in a range of plant products, may exert a variety of pharmacological activities. In this study, we investigated the effect of resveratrol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo, and we found that the pretreatment with resveratrol can effectively protect mice against LPS-induced ALI. Mice were pretreated with 1 mg/kg resveratrol for 3 days before challenging with a dose of 15 mg/kg LPS. The histological result showed that resveratrol can suppress the edema, inflammatory cell infiltration, and alveolar structure damage of lungs in ALI mice, and a decrease in the lung W/D ratio was also observed in mice with resveratrol pretreatment. Additionally, resveratrol markedly decreased the production of inflammatory cytokines, including IL-1β and MIP-1α and prevented the release of nitric oxide (NO) through inhibiting the expression of inducible NO synthase in lung tissues. Furthermore, the pretreatment with resveratrol suppressed the nuclear translocation of NF-κB in lung tissues, which may be partly responsible for its effect on the ALI. In conclusion, the results presented here may suggest resveratrol as a potential therapeutic agent for treating ALI in the future.
The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 03/2011; 294(3):527-32. · 1.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Transcription factors forkhead box (Fox)O1 and pancreatic and duodenal homeobox-1 (PDX-1) are involved in dexamethasone (DEX)-induced dysfunction in pancreatic β-cells. However, the molecular mechanism underlying the regulation of FoxO1 and PDX-1 expression in β-cells treated with DEX is not fully understood. In this study, we found that DEX markedly increased FoxO1 mRNA and protein expression, whereas it decreased PDX-1 mRNA and protein expression in a dose- and time-dependent manner. Further study showed that FoxA2 was involved in regulation of FoxO1 and PDX-1 expression in DEX-induced pancreatic β-cells dysfunction. Interestingly, we demonstrated for the first time that FoxA2 could bind to the FoxO1 gene promoter and positively regulate FoxO1 expression. Moreover, we found that DEX increased the activity of FoxA2 binding to the FoxO1 promoter but decreased the activity of FoxA2 binding to the PDX-1 promoter of RINm5F cells. Knockdown of FoxA2 by RNA interference inhibited FoxO1 expression and restored PDX-1 expression in pancreatic β-cells treated with DEX. However, DEX had no effect on the expression of FoxA2. Together, the results of the present study demonstrated that FoxA2 could dynamically regulate FoxO1 and PDX-1 expression in pancreatic β-cells treated with DEX, which provides new important information on the transcriptional regulation of FoxO1 and PDX-1 in DEX-induced pancreatic β-cells. Inhibition of FoxA2 can effectively protect β-cells against DEX-induced dysfunction.
Endocrinology 03/2011; 152(5):1779-88. · 4.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cyclooxygenase-2 (COX-2) plays important roles in the development of many disease conditions, including pancreatic β-cell dysfunction. Although the processes involved in the transcriptional regulation of COX-2 are well documented, some key elements, especially inhibitory elements, are still unknown. In our previous study, we identified a novel repressor element located in promoter region of mouse COX-2. In this study, we isolated several DNA-binding proteins from NIT-1 cells via DNA affinity chromatography; the most prominent among these proteins was poly (ADP-ribose) polymerase-1 (PARP-1). In this study, gel-supershift assays and chromatin immunoprecipitation assays showed that PARP-1 can bind to the inhibitory element -655/-632 in the promoter region of mouse COX-2 both in vitro and in vivo. Furthermore, overexpression of PARP-1 significantly inhibited promoter activity and decreased COX-2 expression. Conversely, repression of PARP-1 by RNAi upregulated COX-2 expression. These data suggest that PARP-1 plays an important role in the regulation of COX-2 expression via binding to the inhibitory element. Collectively, our findings provide new important information on the transcriptional regulation of COX-2 in pancreatic β-cells.
Archives of Biochemistry and Biophysics 01/2011; 505(1):123-9. · 2.93 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cyclooxygenase-2 (COX-2) plays important roles in the development of many disease conditions, including pancreatic β-cell dysfunction. Although the processes involved in the transcriptional regulation of COX-2 are well documented, some key elements, especially inhibitory elements, are still unknown. In our previous study, we identified a novel repressor element located in promoter region of mouse COX-2. In this study, we isolated several DNA-binding proteins from NIT-1 cells via DNA affinity chromatography; the most prominent among these proteins was poly (ADP-ribose) polymerase-1 (PARP-1). In this study, gel-supershift assays and chromatin immunoprecipitation assays showed that PARP-1 can bind to the inhibitory element −655/−632 in the promoter region of mouse COX-2 both in vitro and in vivo. Furthermore, overexpression of PARP-1 significantly inhibited promoter activity and decreased COX-2 expression. Conversely, repression of PARP-1 by RNAi upregulated COX-2 expression. These data suggest that PARP-1 plays an important role in the regulation of COX-2 expression via binding to the inhibitory element. Collectively, our findings provide new important information on the transcriptional regulation of COX-2 in pancreatic β-cells.
Archives of Biochemistry and Biophysics - ARCH BIOCHEM BIOPHYS. 01/2011; 505(1):123-129.
