The Ah Receptor is Essential for Mediating an Anti-Inflammatory Effect

B. Paige Lawrence, Ph.D. and Michael S. Denison, Ph.D.
Department of Environmental Medicine, University of Rochester and Department of Environmental Toxicology, University of California Davis
NIEHS Grants R01ES0010619, K02ES012409, and R01ES012498

A research team made up of NIEHS grantees from the University of Rochester and the University of California at Davis has discovered a potentially new role for the Ah receptor in treating inflammatory or immunologic disorders. This research adds new information on the diverse functions of the receptor including xenobiotic metabolism, involvement in proper blood vessel formation, and now immune responses.

The team happened upon this discovery while investigating a low-molecular with compound with potent anti-inflammatory activity known as VAF347. The compound is a drug candidate which inhibits allergic lung inflammation. The team demonstrated that VAF347 interacts with the Ah receptor resulting in stimulation of its signaling pathway. Additional experiments in Ah receptor-deficient mice confirmed the connection. These mice are resistant to the compound’s ability to block allergic lung inflammation. The data indicate the Ah receptor protein is an important target of VAF347 and its importance in mediating the anti-inflammatory effects of the compound.

Although the importance of the Ah receptor in mediating the toxicity of various organic compounds is well known, this finding suggests that harnessing the biological activity of the receptor for therapeutic purposes is possible and suggests a new tool for the treatment of inflammatory and immunologic disorders.

Citation: Lawrence BP, Denison MS, Novak H, Vorderstrasse BA, Harrer N, Neruda W, Reichel C, Woisetschläger M. Activation of the aryl hydrocarbon receptor is essential for mediating the anti-inflammatory effects of a novel low-molecular-weight compound. Blood. 2008 Aug 15;112(4):1158-65.