Macrophage Migration Inhibitory Factor (MIF) Overexpression Accelerates Photocarcinogenesis in the Skin

Abstract

The effects of sunlight have fascinated researchers for decades because nearly every living organism on earth is exposed to sunlight, including its ultraviolet (UV) fraction. UV radiation is divided into 3 subtypes, UVA (320–400nm), UVB (280–320nm) and UVC (200– 280nm), each of which has distinct biological effects. Although UVC is blocked by stratospheric ozone, UVB (1–10%) and UVA (90–99%) reach the surface of the earth and cause skin damage (Matsumura and Ananthaswamy, 2002). An increased risk of skin damage from UV light has recently been linked to the decrease in stratospheric ozone (Ma et al., 2001). The health risks associated with ozone depletion are caused by enhanced UVA irradiation in the environment and increased penetration of the UVB light (Tenkate, 1999, Ma et al., 2001). The skin is the body’s main interface with the environment, and is frequently exposed to UV light. Exposure to UV radiation substantially increases the risk of actinic damage to the skin. UV irradiation leads to various acute deleterious cutaneous effects, including sunburn, as well as long-term consequences such as wrinkling, elastosis, irregular pigmentation, telangiectasia and the potential development of skin cancers (Young, 1990). In recent years, there has been increased interest in the contribution of UVA to skin carcinogenesis (Ridley et al., 2009). However, UVB has been demonstrated to be a causal factor for basal cell carcinoma, squamous cell carcinoma, and lentigo maligna in epidemiological and experimental studies, and UVB exposure has been shown to induce the superficial spread of melanoma in humans and other animals (Kraemer et al., 1997). Chronic UVB-induced inflammatory responses, immunosuppression, and direct DNA damage can be correlated with skin tumor formation (Fischer et al., 1999, Pentland et al., 1999). Furthermore, the inability to adequately repair DNA after UVB irradiation can result in the formation of skin cancers (Cleaver et al., 2002) (Figure 1).