BACKGROUND:   The liver X receptors (LXRα and LXRβ) are nuclear receptors activated by oxysterols that are recognized to play an important role in the control of lipid homeostasis.

INNOVATION:   Recent work in the laboratory of Dr. Peter Tontonoz has demonstrated that the LXRs in macrophages activated by oxysterols also exert broad anti-inflammatory effects.

ADVANTAGES
A previously unknown pathway for the innate suppression of the inflammatory response of macrophages may now be exploited. Pharmaceutical compounds may be developed that specifically activate the anti-inflammatory effects of LXRs.

APPLICATIONS
LXR agonists may have utility in the treatment of chronic inflammatory diseases in which activated macrophages play an important role. Such diseases include atherosclerosis, rheumatoid arthritis and glomerulonephritis.

DEVELOPMENT TO DATE:   UCLA investigators found that LXR agonists exert broad anti-inflammatory effects by repressing a cluster of genes involved in the immune response of macrophages, including interleukin (IL)-1β, monocyte chemotactic protein (MCP)-1, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase -2 (COX-2). Evidence indicates that the mechanism of LXR action is repression of transcription regulated by NFκB, the central transcription regulator of the innate immune response. The anti-inflammatory action of LXR was confirmed in vivo in three established mouse models of inflammation.

Related Papers (Selected) Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nature Medicine. 2003 Feb; 9(2):213-218 more... eLiXiRs for restraining inflammation. Nature Medicine. 2003 Feb; 9(2):168 more...

Reference: UCLA Case No. 2003-188

US Publication Number: US-2004-0259948-A1