Barbara L. F. Kaplan, Ph.D.
Department of Basic Sciences
Center for Environmental Health Sciences
College of Veterinary Medicine
PO Box 6100
Mississippi State, MS 39762-6100
- B.S., Environmental Toxicology
University of California, Davis
- Ph.D., Pharmacology and Toxicology
Michigan State University
- Postdoctoral Research Associate
University of Chicago
The focus of my laboratory is to elucidate the mechanisms by which cannabinoid compounds (i.e., those derived from marijuana) alter immune function. Previously we demonstrated that plant-derived cannabinoid compounds suppress T cell-dependent humoral immunity. The mechanism by which this occurs likely involves direct T and B cell effects, in addition to disruption of proteins that mediate T cell-B cell interactions. Interestingly, suppression of T cell function does not occur via either of the currently cloned cannabinoid receptors, CB1 or CB2, but suppression of B cell function is mediated through CB1 and/or CB2.
I am currently focusing on two projects. First, I am characterizing the mechanisms by which plant-derived compounds alter T cell function. Although many reports demonstrate that cannabinoid compounds suppress immune function, there are also reports of cannabinoid-mediated enhancement of immune function. These differential effects, at least in T cells, are related to the magnitude to which the T cells are activated with antigen or other agents. Specifically, we demonstrated that cannabidiol (CBD) and D9-tetrahydrocannabinol (D9-THC) enhance or suppress cytokine production and transcription factor activity in response to supoptimal or optimal cellular activation, respectively. These results suggest that caution should be exercised when using cannabinoids therapeutically to suppress immune function since there are conditions under which they produce the opposite effect.
Second, I am examining the role of CB1, CB2 and the b2 adrenergic receptor (b2AR) in cannabinoid-mediated suppression of B cell function. Neuroimmune interactions are critical for normal immune function and indeed, norepinephrine (NE) binding to b2AR has been shown to enhance antibody production. Since cannabinoids suppress antibody production and suppress neurotransmitter release, I hypothesize that suppression of NE is part of the mechanism by which cannabinoids suppress antibody production. This hypothesis is being tested in a multiple sclerosis (MS) model since cannabinoids have been shown to be effective therapeutics, although the contribution that cannabinoid-mediated suppression of B cell function makes to cannabinoid MS therapies is not understood.
Ngaotepprutaram, T, Kaplan, BLF and Kaminski NE. 2013. Impaired NFAT and NFkB Activation are Involved in Suppression of CD40 Ligand Expression by D9-Tetrahydrocannabinol in Human CD4+ T Cells. Toxicol Appl Pharmacol. In Press.
Ngaotepprutaram, T, Kaplan, BLF, Carney, S, Crawford, R and Kaminski, NE. 2013. Delta-9-tetrahydrocannabinol Suppresses the Primary Immunoglobulin M Response by Human Peripheral Blood B Cells in Association with STAT3 Activation. Toxicology. 310: 84-91.
Karmaus, PWF, Wagner, JG, Harkema, JR, Kaminski, NE and Kaplan, BLF. 2013. Cannabidiol (CBD) Enhances Lipopolysaccharide (LPS)-Induced Pulmonary Inflammation in C57BL/6 Mice. J. Immunotoxicol. 10: 321-328.
Kaplan, BLF. 2013. The Role of CB1 in Immune Modulation by Cannabinoids. Pharmacol Ther. 137: 365-374.
Karmaus, PWF, Chen, W, Crawford, R, Kaplan, BLF, and Kaminski, NE. 2013. D9-Tetrahydrocannabinol Impairs the Inflammatory Response to Influenza Infection: Role of Antigen Presenting Cells and the Cannabinoid Receptors 1 and 2. Toxicol Sci. 131: 419-433.
Chen, W, Kaplan, BLF, Pike, S, Topper, LA, Lichorobiec, NR, Simmons, SO, Ramabhadran, R and Kaminski, NE. 2012. Magnitude of Stimulation Dictates the Cannabinoid-Mediated Differential T Cell Response to HIVgp120. J Leukoc Biol. 92: 1093-1102.
Karmaus, PWF, Chen, W, Kaplan, BLF and Kaminski, NE. 2012. D9-Tetrahydrocannabinol Suppresses Cytotoxic T Lymphocyte Function Independent of CB1 and CB2, Disrupting Early Activation Events. J Neuroimmune Pharmacol. 7: 843-855.
Raman, P, Kaplan, BLF, and Kaminski, NE. 2012. 15-deoxy D12,14 PGJ2-glycerol ester, a Putative Metabolite of 2-Arachidonyl Glycerol and a PPARg Ligand, Modulates NFAT Activity in Activated T cells. J Pharmacol Exp Ther. 342: 816-826.
Simkins, TJ, Janis, KL, McClure, AK, Behrouz, B, Pappas, S, Lehner, A, Kaminski, NE, Goudreau, JL, Lookingland, KJ and Kaplan, BLF. 2012. Comparison of D2 Receptor Regulation and Neurotoxicant Susceptibility of Nigrostriatal Dopamine Neurons in Wild Type and CB1/CB2 Receptor Knockout Mice. J Neuroimmune Pharmacol, 7: 533-538.