Targeting Nuclear Hormone Receptors: PPARα Agonists as Potential Disease-Modifying Drugs for Rheumatoid Arthritis
Figure 3
(a) a hypothetical mechanisms of PPARα interference with glucocorticoid effects. GC/GCR complex binds to specific DNA sites called GRE which results in increased expression of many genes encoding proteins involved in fat, glucose, and protein metabolism. Adverse effects of GC are thought to stem from GRE binding. GC/GCR also down regulates transcription factors NFκB and AP-1 thus suppressing synthesis of inflammatory mediators. (b) PPARα further inhibits NFκB and AP-1 thus enhancing GC anti-inflammatory action. PPARα inhibition of GC/GCR-mediated GRE activation leads to attenuation of GC-induced adverse events. GC: glucocorticoid, GCR: glucocorticoid receptor, GRE: glucocorticoid response element, NFκB: nuclear factor κB, IκB: inhibitor of κB, and AP-1: activator protein 1.
