Ellagic acid and its fermentative derivative urolithin A show reverse effects on the gp91-phox gene expression, resulting in opposite alterations in all-trans retinoic acid-induced superoxide generating activity of U937 cells

Potential role of green tea amino acid l‐theanine in the activation of innate immune response by enhancing expression of cytochrome b558 responsible for the reactive oxygen species‐generating ability of leukocytes

“…To investigate the physiological effects of l ‐theanine on the O 2 − ‐generating activity of leukocytes, we examined its influences on the ATRA‐induced O 2 − ‐generating activity in U937 cells (Figure 1b,c). As shown in our previous reports, 21–25,27 ATRA‐treated U937 cells acquire remarkable O 2 − ‐generating ability upon stimulation with PMA, while untreated U937 cells does generate a negligible level of O 2 − by PMA. As shown in Figure 1b, very interestingly, the ATRA‐induced O 2 − ‐generating activity of U937 cells was remarkably enhanced by the addition of 500 μM l ‐theanine during experimental condition (to ~470% of ATRA‐treated cells).…”

“…These two Lys residues of histone H3 are the typical acetylation sites that participate in transcriptional activation of numerous genes 30–32 . As shown in our previous papers, ATRA remarkably accelerated the acetylation levels of H3K9 residues within chromatin surrounding the promoter region of the gp91‐phox gene, but not those of H3K14 residues 22–24 . By contrast, the acetylation levels of H3K14 residues were enhanced by resveratrol and butein in the presence of ATRA 22,23 .…”

“…In addition, we demonstrated that l ‐theanine enhances the ATRA‐induced O 2 − ‐generating activity via upregulation of acetylation of H3K9 and H3K14 residues followed by transactivation of the gp91‐phox gene. Resveratrol, 22 butein, 23 and urolithin A 24 have the properties to enhance the ATRA‐induced O 2 − ‐generating ability via upregulation of the gp91‐phox gene in U937 cells. In other words, the gp91‐phox gene may be a main target for various phytochemicals having the ability to promote the O 2 − ‐generating ability in U937 cells.…”

“…Monoclonal antihuman p22‐phox antibody (449) was kindly provided by Dr. Roos and Dr. Verhoeven (Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, the Netherlands, respectively). The sources of other antibodies used were described in our previous article 24 …”

“…First‐strand complementary DNA was synthesized from the total RNA using a ReverTra Ace‐α kit (Toyobo, Osaka, Japan). Semiquantitative RT‐PCR was carried out using specific primers for detecting p22‐phox, gp91‐phox, p40‐phox, p47‐phox, and p67‐phox genes as described previously 21–25 . Human GAPDH gene was used as the internal control.…”