REGULATION OF THE HUMAN HEME OXYGENASE 1 GENE BY SOLAR UVA R ADIATION - A POTENTIAL ROLE FOR BACH PROTEINS AND HEME TURNO

Repeated acute (e.g. sunburn) or chronic inflammatory events can lead to permanent tissue damage and disease so that agents which suppress inflammation are used to treat disease. Among the body’s own anti-inflammatory proteins is heme oxygenase 1 which is induced in many types of tissue following damage, including damage by the ultraviolet A component of sunlight. The protein is able to break down heme, a molecule which can have damaging side-effects when in excess and unbound to protein. Understanding how this protein is regulated and how it is able to protect cells and tissues should provide information of value in treating inflammatory disease. We intend to use cells derived and cultured from human skin to study responses to the UVA radiation component of sunlight and will determine the factors and enzymatic pathways involved in the UVA regulation of this inducible anti-inflammatory response. By defining and understanding such pathways, we hope not only to advance our basic knowledge of cell biology but also to facilitate the development of more sophisticated strategies of disease prevention based on controlling the inflammatory response.