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

l-Theanine (N-ethyl- l-glutamine) is an analog of l-glutamine and l-glutamic acid, accounts for up to 50% of all free amino acids in green tea, and elicits an umami taste. As l-theanine also shows various physiological activities including immune response-modifying activities, it is expected to be an excellent health-promoting phytochemical agent. To know the influences of l-theanine on the human innate immune response, we investigated the effect of l-theanine on the superoxide anion (O )-generating system of leukocytes using U937 cells. The O -generating system in leukocytes consists of membrane cytochrome b protein (a complex of p22-phox and gp91-phox proteins) and cytosolic p40-phox, p47-phox, and p67-phox proteins. Addition of 500 μM l-theanine caused remarkable enhancement of the all-trans retinoic acid (ATRA)-induced O -generating activity (to ~470% of ATRA-treated cells), but not l-glutamine and l-glutamic acid. Semiquantitative RT-PCR showed that the transcription level of gp91-phox is significantly increased in ATRA and l-theanine-co-treated cells. Chromatin immunoprecipitation revealed that l-theanine enhances acetylations of Lys-9 and Lys-14 residues of histone H3 within the chromatin surrounding the promoter region of the gp91-phox gene. Immunoblotting demonstrated that membrane cytochrome b proteins remarkably accumulate in ATRA +  l-theanine-treated cells. These results suggested that l-theanine brings about a remarkable accumulation of cytochrome b protein via upregulating the transcription of the gp91-phox gene during leukocyte differentiation, resulting in marked augmentation of the O -generating ability, which is one of the most important functions of leukocytes responsible for the innate immune system.