Marijuana THC treatment led to decreased metabolic functions of Staphylococcal enterotoxin B-activated lymphocytes
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Abstract<p>Studies from our laboratory have shown that Δ9-Tetrahydrocannabinol (THC), an ingredient found in marijuana plant Cannabis sativa, can attenuate acute lung injury induced by Staphylococcus enterotoxin B (SEB). In the current study, we investigated the role of THC on the metabolism of SEB-activated lymphocytes. To this end, we determined metabolic potential of SEB-activated lymphocytes treated with vehicle or THC by performing the Cell Mito Stress Test. The oxygen consumption rate (OCR) in THC-treated cells was decreased when compared to vehicle-treated group whereas the extracellular acidification rate (ECAR) was similar in both the groups. Specifically, electron transport chain inhibitors namely, oligomycin, FCCP and rotenone+antimycinA were added to measure ATP-linked respiration, maximal respiration and non-mitochondrial respiration, respectively. THC treatment led to a significant decrease in the basal respiration, ATP production, proton (H+) leak, maximal respiration, spare respiratory capacity and nonmitochondrial respiration. We also performed the Mito Fuel Flex assay to measure the dependency, capacity and flexibility of cells to oxidize glucose, glutamine and fatty acids. Treatment with inhibitors, BPTES and etomoxir showed a decline in the OCR in SEB+vehicle treated cells demonstrating that glutamine and/or fatty acids serve as major source of fuel in these cells when compared to SEB+THC treated group. However, when UK5099 was added, THC- and vehicle-treated cells showed a reduced response thereby indicating that glucose dependency was similar in both the groups. Together, THC modulates metabolic functions of activated lymphocytes which may affect their signaling, differentiation and toxicity.</p>
