delta 9-Tetrahydrocannabinol (THC) causes the variable expression of IL2 receptor subunits.
Previously, we reported that the cannabinoid delta 9-tetrahydrocannabinol (THC) suppressed interleukin 2 (IL2)-induced proliferation of a cloned, natural killer-like cell line (NKB61A2) and decreased the number of high- and intermediate-affinity IL2 binding sites. However, the surface expression of interleukin 2 receptor alpha (IL2R alpha) chain, as measured by flow cytometry, was increased rather than decreased by THC treatment. This suggested that the drug-induced deficiency in IL2 binding and cell activation involved a defect in the cell-surface expression of IL2R subunits other than the alpha chain. Because the IL2 receptor complex is composed of alpha, beta and gamma chains, we examined the effect of THC treatment on the expression of these chains. In a result consistent with our previous findings, we observed that treatment of NKB61A2 cells with THC increased the cellular immunoprecipitable IL2R alpha protein (p55) and mRNA. Furthermore, the cellular production of IL2R beta chain protein (p75) and mRNA, determined by immunoprecipitation and Northern blotting, respectively, was also increased. The mRNA stability assay showed that THC increased the stability of IL2 beta mRNA, and nuclear run-on experiments suggested that the increase in subunit production was not due to a drug effect on gene transcription. The IL2R gamma chain was also affected by THC treatment in that Northern blotting studies showed a drug-induced decrease in the cellular level of gamma chain mRNA. In addition, THC treatment decreased the 125I-labeled IL2 internalization under high-affinity binding conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhu
W
W
Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa, USA.
Igarashi
T
T
Friedman
H
H
Klein
T W
TW
D000818:Animals; D002460:Cell Line; D013759:Dronabinol / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000187:drug effects* / Q000235:genetics
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D013759:Dronabinol