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Differential effects of arsenic on cutaneous and systemic immunity: focusing on CD4+ cell apoptosis in patients with arsenic-induced Bowen's disease
- Source :
- Carcinogenesis. 30(6)
- Publication Year :
- 2009
-
Abstract
- 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 CD4+ 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 CD4+ cells as compared with control subjects. However, the CD4+ 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 CD4+ cells and increase the soluble Fas ligand (sFasL) production from keratinocytes. This sFasL-containing keratinocyte supernatant was able to induce comparable CD4+ 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 CD4+ cells. Our findings suggested that systemically, the percentage of CD4+ cells was decreased in the peripheral blood of As-BD patients. These residual CD4+ cells were less susceptible to arsenic-induced apoptosis. However, once infiltrated into the As-BD lesions, the selective CD4+ cell apoptosis might be mediated by FasL from keratinocytes. This additional tumor-anti-immune phenomenon present in the cutaneous environment provides a reasonable explanation for frequent occurrence of arsenic cancers in the skin.
- Subjects :
- CD4-Positive T-Lymphocytes
Keratinocytes
Male
Cancer Research
Fas Ligand Protein
Skin Neoplasms
Lymphocyte
Apoptosis
Bowen's Disease
Biology
Fas ligand
Arsenic
Immune system
medicine
Humans
Cells, Cultured
Aged
Bowen's disease
Arsenic toxicity
General Medicine
Middle Aged
medicine.disease
medicine.anatomical_structure
Cell Transformation, Neoplastic
Immunity, Active
Immunology
Female
Tumor necrosis factor receptor 1
Keratinocyte
Subjects
Details
- ISSN :
- 14602180
- Volume :
- 30
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....b14db839942b8a2c0beac787b79d4952