Hepatitis B Virus X Protein Induces Expression of Fas Ligand Gene through Enhancing Transcriptional Activity of Early Growth Response Factor

Yoo, Young-Gun; Lee, Mi‐Ock

doi:10.1074/jbc.m401290200

Cited by 51 publications

(34 citation statements)

References 52 publications

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“…Interestingly, EGR3 but not EGR1 was shown to increase FASLG expression in T cells and fibroblasts (Mittelstadt & Ashwell 1998, Yoo & Lee 2004; therefore, the effect of DON on FASLG expression may be mediated in part through EGR3. E 2 is a major determinant of follicle development and decreases granulosa cell apoptosis in rodents in vivo (Billig et al 1993).…”

Section: Discussionmentioning

confidence: 99%

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Guerrero-Netro¹,

Chorfi²,

Price³

2015

Reproduction

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Mycotoxins can reduce fertility and development in livestock, notably in pigs and poultry, although the effect of most mycotoxins on reproductive function in cattle has not been established. One major mycotoxin, deoxynivalenol (DON), not only targets immune cells and activates the ribotoxic stress response (RSR) involving MAPK activation, but also inhibits oocyte maturation in pigs. In this study, we determined the effect of DON on bovine granulosa cell function using a serum-free culture system. Addition of DON inhibited estradiol and progesterone secretion, and reduced levels of mRNA encoding estrogenic (CYP19A1) but not progestogenic (CYP11A1 and STAR) proteins. Cell apoptosis was increased by DON, which also increased FASLG mRNA levels. The mechanism of action of DON was assessed by western blotting and PCR experiments. Addition of DON rapidly and transiently increased phosphorylation of MAPK3/1, and resulted in a more prolonged phosphorylation of MAPK14 (p38) and MAPK8 (JNK). Activation of these pathways by DON resulted in time-and dose-dependent increases in abundance of mRNA encoding the transcription factors FOS, FOSL1, EGR1, and EGR3. We conclude that DON is deleterious to granulosa cell function and acts through a RSR pathway.

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Section: Discussionmentioning

confidence: 99%

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Guerrero-Netro¹,

Chorfi²,

Price³

2015

Reproduction

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show abstract

“…Most immune privilege effects were found to be the result of altered gene expression or biological changes in cancer cells (38,39). Indeed, FasL-associated tumor-anti-immune effects have been reported in different tumors, including colon cancers (38), ovarian carcinoma (40), hepatoma (41), breast cancer and head and neck malignancies (39,42). In our present study, we unveiled that arsenicinduced FasL-associated tumor-anti-immune phenomenon is also present at As-BD lesions between keratinocytes and CD4þ cell.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of arsenic on cutaneous and systemic immunity: focusing on CD4+ cell apoptosis in patients with arsenic-induced Bowen's disease

Liao

Lan

et al. 2009

Carcinogenesis

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Bowen's disease (BD), a carcinoma in situ of the skin, has been identified as an early lesion in arsenic carcinogenesis. Patients with arsenic-induced Bowen's disease (As-BD) showed both cutaneous and systemic immune dysfunctions. We set out to evaluate the interactions between keratinocytes and lymphocytes in the context of As-BD carcinogenesis. Our results showed that As-BD lesions demonstrated a significant dermal CD41 cell, an essential regulator of proper tumor immunity, undergoing apoptosis. In addition, it was found that the As-BD patients have lower percentage of peripheral CD41 cells as compared with control subjects. However, the CD41 cells from As-BD patients were less susceptible to arsenic-induced apoptosis, due to reduced tumor necrosis factor receptor 1 expression. Interestingly, arsenic was found to induce Fas expression on CD41 cells and increase the soluble Fas ligand (sFasL) production from keratinocytes. This sFasLcontaining keratinocyte supernatant was able to induce comparable CD41 cell apoptosis for both patients and controls. Using immunofluorescent staining, increased FasL was observed in keratinocytes of As-BD lesions and Fas was expressed among infiltrating CD41 cells. Our findings suggested that systemically, the percentage of CD41 cells was decreased in the peripheral blood of As-BD patients. These residual CD41 cells were less susceptible to arsenic-induced apoptosis. However, once infiltrated into the As-BD lesions, the selective CD41 cell apoptosis might be mediated by FasL from keratinocytes. This additional tumoranti-immune phenomenon present in the cutaneous environment provides a reasonable explanation for frequent occurrence of arsenic cancers in the skin.

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“…It was reported that moderate expression level of HBx can inhibit liver regeneration in HBx-expressing transgenic mice after partial hepatectomy [6] . HBx stimulates expression of FasL, which plays an important role in cell's escaping from immune surveillance by inducing apoptosis of T cell bearing Fas [7,8] . HBx boosts cell survival by abrogating Bcl-2-mediated cell protection [9,10] .…”

Section: Cell Apoptosis Assaymentioning

confidence: 99%

Apoptosis and its pathway in X gene-transfected HepG₂cells

Lin

Chen²,

Li³

et al. 2005

WJG

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Hepatitis B Virus X Protein Induces Expression of Fas Ligand Gene through Enhancing Transcriptional Activity of Early Growth Response Factor

Cited by 51 publications

References 52 publications

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Differential effects of arsenic on cutaneous and systemic immunity: focusing on CD4+ cell apoptosis in patients with arsenic-induced Bowen's disease

Apoptosis and its pathway in X gene-transfected HepG₂cells

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Hepatitis B Virus X Protein Induces Expression of Fas Ligand Gene through Enhancing Transcriptional Activity of Early Growth Response Factor

Cited by 51 publications

References 52 publications

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Differential effects of arsenic on cutaneous and systemic immunity: focusing on CD4+ cell apoptosis in patients with arsenic-induced Bowen's disease

Apoptosis and its pathway in X gene-transfected HepG2cells

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Apoptosis and its pathway in X gene-transfected HepG₂cells