-
[show abstract]
[hide abstract]
ABSTRACT: Hepatitis C virus (HCV) infection is still a major global health issue despite decades of research. The liver-specific microRNA-122 (miR-122) can stimulate HCV replication/translation in vitro, indicating that miR-122 contributes to pathogenesis of HCV. However, it remains controversial whether interferon (IFN) inhibits HCV via modulating miR-122 expression. The underlying mechanism of ribavirin (RBV) in enhancing IFN treatment for HCV patients has yet to be explored. We investigated the relationship between miR-122 expression and anti-HCV activity of IFN beta in combination with RBV in vitro, due to difficulty accessing an HCV animal model. Upregulation of ISG54 mRNA or cytostatic effect was detected in Huh7 and HCV replicon cell lines in response to IFN beta or RBV stimulation, respectively. It was found that IFN beta and/or RBV suppressed miR-122 expression marginally, with a synergetic anti-HCV effect between IFN beta and RBV. Marginal modification of other miRNAs was also observed in these cell lines, using miRNA array following IFN beta and RBV treatment. Taken together, our data suggest that miRNAs are not crucial in anti-HCV action, following IFN beta and/or RBV stimulation in vitro.
International Journal of Molecular Medicine 06/2010; 25(6):853-9. · 1.98 Impact Factor
-
Yi Wang,
Hong-Xin Zhang,
Yue-Ping Sun,
Zi-Xing Liu,
Xue-Song Liu,
Long Wang,
Shun-Yuan Lu,
Hui Kong,
Qiao-Ling Liu,
Xi-Hua Li,
Zhen-Yu Lu,
Sai-Juan Chen,
Zhu Chen, Shi-San Bao,
Wei Dai,
Zhu-Gang Wang
[show abstract]
[hide abstract]
ABSTRACT: RIG-I (retinoid acid-inducible gene-I), a putative RNA helicase with a cytoplasmic caspase-recruitment domain (CARD), was identified as a pattern-recognition receptor (PRR) that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I(-/-) mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I(-/-) mice are viable and fertile. Histological analysis shows that Rig-I(-/-) mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer's patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation of T-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein alpha i2 subunit (G alpha i2) in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated G alpha i2 expression. Moreover, G alpha i2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of G alpha i2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of G alpha i2 and disturbed T-cell homeostasis.
Cell Research 11/2007; 17(10):858-68. · 8.19 Impact Factor
-
Yi Wang,
Hong-Xin Zhang,
Yue-Ping Sun,
Zi-Xing Liu,
Xue-Song Liu,
Long Wang,
Shun-Yuan Lu,
Hui Kong,
Qiao-Ling Liu,
Xi-Hua Li,
Zhen-Yu Lu,
Sai-Juan Chen,
Zhu Chen, Shi-San Bao,
Wei Dai,
Zhu-Gang Wang
[show abstract]
[hide abstract]
ABSTRACT: RIG-I (retinoid acid-inducible gene-I), a putative RNA helicase with a cytoplasmic caspase-recruitment domain (CARD), was identified as a pattern-recognition receptor (PRR) that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I−/− mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I−/− mice are viable and fertile. Histological analysis shows that Rig-I−/− mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer's patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naïve T cells, indicating an important role for Rig-I in the regulation of T-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein αi2 subunit (Gαi2) in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated Gαi2 expression. Moreover, Gαi2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of Gαi2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of Gαi2 and disturbed T-cell homeostasis.Keywords: Rig-I knockout mice; colitis; Peyer's patches; T-cell homeostasis; Gαi2 expression
Cell Research 09/2007; 17(10):858-868. · 8.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To study the effect of GMCSF-absence on the rate of wound healing and neovascularization during wound repair.
30 wild type (WT) mice and 30 GMCSF- absence mice (GMCSF-KO) were obtained. They were received full thickness skin wound (0.8 cm x 0.8 cm) in each side of midline after deeply anesthesia. In the different post-injury time points, the wound sites were digitally photographed to calculate the percentage of wound closure by using computer image analyses software. The wound specimens were also obtained dynamically for immunohistological analysis of CD31 at wound site.
The analysis of the wound closure showed that wound healing in GMCSF-KO mice was delayed significantly comparing with that in WT mice from the day 3 post-wounding. At days 7 and 10 after wounding significantly more numbers of blood vessels were formed in the WT controls compared to the GMCSF-KO mice.
GMCSF-absence inhibits neovascularization during wound repair and leads to the delay of wound healing.
Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery 06/2007; 23(3):233-5.
-
[show abstract]
[hide abstract]
ABSTRACT: To study the influence of FasL overexpression in transgenic mice on the Sertoli cell immune response to testicular infection.
Ureaplasma urealyticum (UU) was directly injected into bladders of FasL transgenic mice and wild-type mice respectively, to mimic an ascending infection pathway. At week 1, 2 and 3 after injection, respectively, the mice were put to death to observe the pathological alterations in testis section. And at the same time the differences of FasL, TGF-beta, IL-1alpha and IL-6 expressions on Sertoli cells were compared by immunohistochemical staining between wild mice and transgenic mice before and after infection, respectively. The high-purified Sertoli cells were isolated from the testis tissue of wild-type mice, comparing apoptotic capability of Fas(+) Jurkat cells mediated by FasL(+) Sertoli cells of wild control and wild UU-infected groups.
The pathological changes of testis tissue from transgenic mice were more serious as compared with wild-type mice and the model of cytokines secreted by sertoli cells was distinctive between the two kinds of mice. The UU-infected Sertoli cells increased Fas(+) Jurkat cell apoptosis.
FasL overexpression can influence the cytokine's secretion in the process of anti-infection immunity and further affects the immune balance of testis locality. Not all FasL over expression is benefit to body's anti-infection immune response.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 08/2004; 20(4):456-60.
-
[show abstract]
[hide abstract]
ABSTRACT: Objective To study the immune regulative function of Sertoli cell on testis local infec-tion Methods Ureaplasma urealyticum (UU) was directly injected into bladders of FasL transgenic mice and wild-type mice, which mimicked an ascending infectious way. At week 1, 2 and 3 after injection respectively, the mice were killed to observe the patho-logical alterations in testis section. And at the same time cytokines was tested by immunohistochemistry. Comparison of levels of FasL, TGF-β, IL-1α, and IL-6 between UU-infected and control groups of wild mice and FasL transgenic mice was made respectively. Then the capability of Sertoli cell (FasL +) to mediate apoptosis of Fas + cells between wild control and wild UU-infected groups was analyzed. Results The pathological changes of testis in FasL transgenic mice were more seri-ously compared with wild counterpart and the changing mode of cytokines secreted by Sertoli cells were different between the two kinds of mice. The UU-infected Sertoli cells increased Fas + Jurkat cell apoptosis. Conclusions High expression of FasL in FasL transgenic mice can influence the cytokines secretion during anti-infection, thus affecting the testis immune response to infection and immune balance. The high expression of FasL is not beneficial for body's anti-inflection immune response.
Journal of Reproduction and Contraception 01/2004; 15:209-218.
