Molecular mechanism of apoptotic lymphocytes infiltrated in arsenic-induced Bowen's disease
Date Issued
2006
Date
2006
Author(s)
Ho, Chun-Hsuan
DOI
zh-TW
Abstract
Endemic arsenic-induced cancers, ex: skin cancer, bladder cancer, kidney cancer, lung cancer, colon cancer and liver cancer…etc, develop frequently over the highly arsenic-polluted areas in the southwestern Taiwan. In skin tissue, keratinocytes are the target cell of arsenic intoxicity. The dermatologic presentations of chronic arsenism include hyper-pigmentation, hyper-keratinization and malignancy. Among arsenic-induced skin cancer, bowen’s disease, a kind of carcinoma in situ, is the most common and an endemic environmental disease with specificity. The pathological features of arsenic-induced bowen’s disease are: (1) epidermal proliferation (2) loss of cell polarity and atypical keratinocytes (3) massive lymphocytic infiltration in the dermis (4) intra-lesional apoptotic keratinocytes. However, we discovered the characteristic apoptosis of lymphocytes infiltrated in the arsenic-induced bowen’s disease, that never mentioned in the documents before. Both of the underlying pathogenesis and the interaction between keratinocyte and lymphocyte are still unknown and need further investigation. Those are also the goals of this study. In the past, the effects of arsenic to keratinocytes had been well-studied. Now, we have known –
1. At low concentration（0.1∼1μM）, arsenic could induce the proliferation of keratinocytes via control the expression of cell-cycle regulatory proteins, ex:cyclinD1/CDK4 of G1 phase, cyclinA/CDK2 of S phase and cyclinB1/CDK1 of G2 phase via NF-κB.
2. At high concentration（> 1μM）, arsenic turn to activate Fas/Fas ligands by AP-1 and inhibit NF-κB, that could lead into the apoptosis of keratinocytes.
3. Arsenic could promote the macrophages to release TNF-α and induced the apoptosis of CD4+ T cell in the peripheral blood via the regulation of TNF receptor-1
4. Arsenic-treated keratinocytes induced the apoptosis of CD4+ T cell via activation of Fas/Fas ligands
On the contrary, according to the clinical data, the CD4+ T cell in the peripheral blood of the patients with chronic arsenism is more resistant to the arsenic cytotoxicity after long-term adaptation. Hence, we speculated that the apoptosis of lymphocytes infiltrated in the arsenic-induced bowen’s disease is not directly caused by the toxicity of arsenic, but the other mechanism. So the hypothesis of this study is that the cancer cell of bowen’s disease could induce the apoptosis of CD4+ T cell via activation of Fas/Fas ligands. We will confirm this assumption through three parts of study designs, including 1. in vivo 2. in vitro 3. in organotypic culture. Our goal is to clarify the molecular mechanism of apoptotic lymphocytes infiltrated in arsenic-induced Bowen’s disease and the role of immune defense in skin cancer.
Subjects
淋巴球
砷
凋亡
arsenic
lymphocyte
apoptosis
SDGs
Type
text
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