The n-BuOH subfraction of Phellinus linteus induces the expression of heme oxygenase-1 through the PKCd/Nrf2/ARE signaling in RAW264.7 cells

The n-BuOH subfraction of Phellinus linteus induces the expression of heme oxygenase-1 through the PKCd/Nrf2/ARE signaling in RAW264.7 cells

  It has been reported that heme oxygenase-1 (HO-1) mediates the anti-inflammatory activity of the n-BuOH subfraction (PL) prepared from fruiting bodies of Phellinus linteus. This continuing work aimed to elucidate the signaling pathway to the up-regulation of HO-1 by PL. In RAW264.7 macrophage cells, PL was able to enhance phosphorylation of protein kinase C δ (PKCδ), but not PKCα/βII, in a time-dependent manner. PL-induced HO-1 expression was dramatically released by GF109203X, a general inhibitor of PKC, and rottlerin, a specific PKC δ inhibitor but not by G6976, a selective inhibitor for PKCα/βII. Additionally, PL treatment resulted in a marked increase in antioxidant response element (ARE)-driven transcriptional activity, which was dependent on PKCδ but not PKCα. An increase by PL treatment in the ARE-driven transcriptional activity was further enhanced by Nrf2, whereas it was diminished by Keap. The present findings indicate that P. linteus induces HO-1 expression though the PKCδ/Nrf2/ARE signaling pathway.