Analysis of the effects of chronic UV exposure on cutaneous neuroinflammatory responses

The involvement of the nervous system in the induction and maintenance of skin diseases such as psoriasis and atopic dermatitis has long been suspected and many data point to the nervous systems`s role in skin diseases. The clinically symmetric distribution of skin lesions and stress-induced exacerbations of diseases as well as the induction of skin lesions by local traumatization and the remission of psoriatic plaques after nerve sectioning suggest involvement of the nervous system in the pathophysiology of these skin diseases. Clues to a cross-talk between the peripheral nervous system and the immune system within the skin include the close contact between peripheral afferent sensory nerve endings extending directly into the epidermis and keratinocytes and Langerhans cells, the presence of neuropeptide receptors on immunologically competent cells, and the effects of neuropeptides on contact hypersensitivity and delayed-type hypersensitivity reactions. Exposure to ultraviolet radiation has a significant impact on the physiology and pathophysiology of the skin. At high doses, UV can induce inflammation, immunosuppression, and skin cancer. Soluble proinflammatory as well as immunosuppressive mediators are generated by, and released from, epidermal and dermal cells in irradiated skin. In addition, neuropeptides may be released from the peripheral endings of sensory nerves during the UV-induced sunburn reaction. Yet, despite its harmfulness to the skin, UV irradiation is also a valuable tool in the treatment of skin diseases. Interestingly, many of those skin diseases in which the nervous system may be involved respond to UV therapy, and the therapeutic effects of UV light can be obtained with suberythemogenic doses, Therefore, the main goal of the proposed studies is to examine the effects of chronic UV exposure, with suberythemogenic doses and treatment schedules as used in phototherapy, on the mediators and the function of cutaneous afferent nerve fibers, as well as on the density of the dermal and epidermal innervation in the skin of mice. The ability of sunscreens to prevent photodamage to the cutaneous neurosensory system will be determined and compared to the potency of these sunscreens to protect against sunburn. In addition, the use of wild-type animals and animals with specific defects in their neurosensory system will enable us to assess the effect of chronic UV exposure on immune responses mediated by the cutaneous neurosensory system.