Apoptosis in physiological and pathological skin: implications for therapy
1Department of Radiology, Rheinische Friedrich-Wilhelms University of Bonn, Germany. i.boehm@uni-bonn.de
Abstract:
Apoptosis is an inducible suicide program that occurs in all phases of multicellular as well as in protozoa life and gains more and more importance in all medical disciplines. It is required for normal ontogenesis, organ and tissue remodeling, function of the immune system, prevention of inappropriate cellular proliferation and of survival of inappropriate mutations. Thereby apoptosis represents the key event which guarantees differentiation and maintenance of homeostasis. Terminal differentiation seems to be a special form of apoptosis. Dysregulated apoptosis is associated with various pathological conditions, including inflammation, and cancer. Acanthosis, the hallmark of psoriatic skin, is an example for diminished epidermal apoptosis. Defects in termination of inflammatory reactions occur in atopic dermatitis. Lupus erythematosus may arise due to disturbed apoptosis on several check points of the apoptosis cascade. Experimental evidence suggests a role for Bcl-2 and CD95L in the inhibition of programmed cell death in UV-induced skin cancer or malignant melanoma cells. Thus, it leads to survival of malignant cell clones. The slow growth of basal cell carcinomas is due to an increased apoptosis to mitosis ratio. Spontaneous regression of tumors is associated with increased apoptotic rates. Malignant melanoma cells characteristically show different anti-apoptotic strategies which underscore its aggressive behavior and its refractory towards classic therapeutic regimens. Additionally, induction of apoptosis in tumor infiltrating immune cells seems to be a strategy by which the tumor escapes from an immunological attack (tumor counter-attack). Since apoptosis is either absent or altered under pathological conditions therapeutic procedures should correct this. Established therapies like dithranol, vitanin-D3 analogs, low-dose methotrexate, induce apoptosis. Future treatment regimens like vaccine and gene therapy are designed to selectively induce apoptosis. Therefore, pharmacological agents and therapeutic strategies interfering with disrupted apoptosis regulation could improve the therapeutic arsenal in the future.
Insights
Apoptosis, or programmed cell death, is crucial for health but its dysregulation contributes to diseases like cancer. Therapies targeting apoptosis aim to restore cellular balance and improve treatment outcomes.
Area of Science:
- Cell Biology
- Immunology
- Dermatology
Background:
- Apoptosis, a programmed cell death, is vital for multicellular life, regulating development, immunity, and preventing mutations.
- Dysregulated apoptosis is implicated in various diseases, including cancer, inflammatory conditions like atopic dermatitis, and autoimmune disorders such as lupus erythematosus.
- Specific molecular pathways, including Bcl-2 and CD95L, are involved in inhibiting apoptosis in conditions like skin cancer.
Purpose of the Study:
- To highlight the critical role of apoptosis in maintaining homeostasis and its dysregulation in pathological conditions.
- To explore the involvement of apoptosis in skin diseases, cancer, and immune responses.
- To discuss current and future therapeutic strategies aimed at correcting apoptosis defects.
Main Methods:
- Review of existing literature on apoptosis.
- Analysis of apoptosis's role in specific diseases (psoriasis, atopic dermatitis, lupus, skin cancer).
- Examination of molecular mechanisms inhibiting apoptosis in cancer cells.
Main Results:
- Diminished epidermal apoptosis contributes to acanthosis in psoriasis.
- Defects in inflammatory reaction termination are seen in atopic dermatitis.
- Malignant melanoma cells employ anti-apoptotic strategies, contributing to treatment resistance.
- Tumors can evade immune attack by inducing apoptosis in immune cells.
Conclusions:
- Correcting dysregulated apoptosis is a key therapeutic goal for various diseases.
- Established and novel therapies (e.g., dithranol, gene therapy) aim to induce or modulate apoptosis.
- Targeting apoptosis pathways offers promising strategies for future cancer and inflammatory disease treatments.
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