I. Field of the Invention
The present invention relates to the fields of cell biology and biochemistry generally, and more specifically to the use nucleotide release as a measure of inflammatory action of a chemical. In addition, the present invention relates to the prevention and treatment of inflammation using nucleoside triphosphate diphosphohydrolase (NTPDase) activity, and includes protein-based and gene-based therapies. The invention also provides methods for screening candidate compounds for NTPDase modulatory activity. Furthermore, the invention provides methods for treating and/or preventing hyperactive immune disorders using NTPDase inhibitors or P2-receptor inhibitors. Methods for screening for modulators of NTPDase-mediated immune responses are also provided.
II. Brief Description of the Prior Art
Irritant contact dermatitis, the most frequent type of skin inflammation, results from contact with a substance that chemically damages the skin. As new chemicals are constantly being developed for use in many commercial products, including cosmetics, drugs, clothes, diapers, paints, soaps, shampoos, cleaning solutions, detergents, adhesives, food and food packaging, contraceptives, household cleaners, automobile interiors and parts, recycled paper, garden chemicals and other household products, cases of irritant contact dermatitis are on an exponential rise. Accidental, occupational or consumer-based exposure to such products can result in acute or chronic irritant contact dermatitis—the most common occupational health problem, and the most common skin disorder, in the United States.
Signs and symptoms of contact dermatitis can include skin inflammation characterized by redness, bumps, blisters, scaling, swelling, oozing, crusting, itching, and pain. These symptoms often occur at the site of contact, which is frequently the hands, arms, or legs, or face, but can occur elsewhere on the skin as well.
In spite of the rise in the number of cases of irritant contact dermatitis, efforts to develop assays which accurately predict the irritant potential of various chemicals have not been successful. Thus, there remains a need to develop accurate and sensitive assays for predicting irritant potential, as well as methods for the treatment thereof.
In addition to irritant contact dermatitis, diseases that are caused by hyperactivity of the immune system also are of concern. These diseases include a spectrum of allergic and autoimmune conditions that are associated with immunologically-mediated damage to the host tissue. Allergic contact dermatitis is another form of dermatitis which is one of the leading occupational hazards in the United States. Other allergic conditions include atopic dermatitis, hay fever, asthma and the like. Examples of autoimmune diseases include multiple sclerosis, rheumatoid arthritis, Crohn's disease, systemic lupus eryrthmatosus (SLE), etc. These diseases afflict many individuals and cause significant morbidity and mortality. Treatments for autoimmune diseases generally include immune suppression. Unfortunately, generalized immune suppression often results in increased incidence of infections and malignancies. Therefore, treatment of patients with an immunological disorder is at the cost of placing the patient at a risk of developing other, possibly life threatening, diseases.
What is required in the art is the identification of molecular targets of the immune system that play a role in hyperactive immune conditions and the development of screening methods to identify agents that can modulate these molecular targets. These agents can then be used therapeutically to treat/prevent immune hyperactivity.