Alteration of Mevalonate Pathway in Rat Splenic Lymphocytes: Possible Role in Cytokines Secretion Regulated by L-Theanine

Abstract

L-Theanine is a nonprotein amino acid in tea, and its immunomodulatory function has been confirmed. This study aimed to investigate the effect of L-theanine addition on cytokines secretion in rat splenic lymphocytes and explore its potential immunomodulatory effects on the mevalonate biosynthetic pathway. Our results showed that L-theanine treatment did not influence the proliferation and division indexes of the splenic lymphocytes subsets. Interestingly, L-theanine treatment had regulated the contents of IFN-γ, IL-2, IL-4, IL-10, IL-12, and TNF-α (P < 0.001) except IL-6 and upregulated the mRNA and protein expression of Ras-related protein Rap-1A (Rap1A), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and farnesyl diphosphate synthase (FDPs) (P < 0.001). Additionally, there was a positive correlation between Rap1A and HMGCR proteins expression and IFN-γ, IL-4, and IL-6 levels. In conclusion, L-theanine regulated the secretion of cytokines probably by activating expression of Rap1A and HMGCR proteins involved in the mevalonate biosynthetic pathway in rat splenic lymphocytes. Therefore, L-theanine might be a promising potential drug candidate as immunopotentiator.

L-Theanine and Immunity: A Review

“…In addition, Rap1A and HMGCR protein expression was positively correlated with IFN-γ, IL-4, and IL-6 levels. These results suggested that L-theanine may regulate cytokine secretion in rat splenic lymphocytes by activating the expression of Rap1A and HMGCR proteins involved in the mevalonate biosynthesis pathway [62].…”

“…The intake of alkylamines through diet (L-theanine) and medicines (such as bisphosphonates) inhibits the MEP and increases the accumulation of IPP so that Vγ2Vδ2T cells are in the primed and ready state, which can rapidly respond and proliferate in the face of pathogens and expand up to 50 times in the peripheral blood [53]. It has also been proven that L-theanine regulates the secretion of cytokines in spleen lymphocytes by activating the expression of Rap1A and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) proteins in the MEP and is a promising immunostimulant [62].…”

L-Theanine: A Unique Functional Amino Acid in Tea (Camellia sinensis L.) With Multiple Health Benefits and Food Applications

“…In the SD rat models, daily intragastric administration of L-theanine solution (400 mg/kg) could increase the weight of the spleen, modify the balance of Th1/Th2 cytokines, reduce the level of serum corticosterone, increase the level of dopamine and 5-HT in the brain, and regulate the mRNA expression of phospholipase C isomers in the heart, finally improving the immune function ( 92 ). Moreover, in another study, L-theanine effectively regulated the secretion of cytokines such as IFN-γ, IL-2, IL-4, IL-10, IL-12, and TNF-α except for IL-6 by activating the mRNA and protein expression of Ras-related protein Rap-1A (Rap1A), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and farnesyl diphosphate synthase (FDPs) in the mevalonate synthesis pathway of rat splenic lymphocytes ( 93 ). In addition, L-theanine treatment decreased the mRNA expression of Toll-like receptors (e.g., TLR-2 and TLR-4) and cytokines (e.g., IFN-α, IFN-γ, and IL-2) in broilers ( 94 ).…”

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

“…10 Along with other phytochemicals in green tea, Ltheanine also shows attractive biological activities, such as antiaging, antianxiety, anticancer, anti-inflammatory, antimicrobial, antioxidant, growth-promoting, and hepato-protective activities. 11 Regarding the immune system, L-theanine is involved in enhancement of γδ T-cell function, 12,13 improvement of Th1/Th2 cytokine balance, 14 regulation of cytokine secretion, 15 and control of immune function by binding to cannabinoid receptor. 16 However, both the physiological effects of L-theanine on the immune system and its action mechanisms remain unclear.…”