FIG. 7.

Network of 15d-PGJ₂ and the Nrf2-Keap1 pathway in carrageenan-induced pleurisy. 15d-PGJ₂ is generated in pleural macrophages during carrageenan-induced pleurisy and is known to directly inhibit NF-κB activity and also to act as a ligand for PPARγ. This study shows that 15d-PGJ₂ activates the Nrf2-Keap1 pathway through covalent binding to Keap1. Nrf2 induces HO-1 and PrxI expression as well as other ARE-regulated genes in macrophages (green). The upregulation of PrxI appears to inhibit NF-κB, TNF-α, and the β-tautomerase activity of MIF, thus modulating the inflammation process. On the other hand, HO-1 is known to inhibit the expression of TNF-α through CO production.