The primary focus of my research is to determine the mechanism by which cannabinoid compounds (marijuana) modulate immune function. Previously we have demonstrated that plant-derived cannabinoid compounds suppress the T cell growth factor interleukin-2 (IL-2) at the transcriptional level and that this inhibition involves decreased nuclear factor of activated T cell (NFAT) activity. Interestingly, in vitro, suppression of IL-2 does not occur via either of the currently cloned cannabinoid receptors, CB1 or CB2, suggesting that other receptors must be involved. With the current debate as to whether marijuana should be approved for medical use, it is critical to understand the effects of these compounds on the immune system.

Current Projects
I am currently focusing on two projects. 

First, I am characterizing the mechanisms by which cannabidiol, a non-psychoactive plant-derived cannabinoid, modulates immune function. Cannabidiol will either suppress or stimulate cytokine production (IL-2, IFN-gamma) depending on the magnitude of lymphocyte activation. Interestingly, cannabidiol, in the absence of activation, increases intracellular calcium.  The intracellular targets of cannabidiol and lymphocyte activation are being investigated.

Second, I am determining the effect of two plant-derived cannabinoids, cannabidiol and delta-9-tetrahydrocannabinol, on pulmonary inflammation. Cannabinoid compounds have been described as anti-inflammatory, yet there are instances in which they possess modest stimulatory effects on inflammatory mediators.
 
Achievements since 2001
Michigan State University Respiratory Research Initiative Group Seed Grant, February, 2008

American Association of Immunologists Junior Faculty Travel Award , March, 2007

Michigan State University Respiratory Research Initiative Group Seed Grant, November, 2006

National Food Safety and Toxicology Center Research Expense Award, May, 2006

Publications since 2001
Lu, Haitian, Kaplan, Barbara L.F., Ngaotepprutaram, Thitirat, and Kaminski, Norbert E. 2008.  Suppression of T Cell Co-stimulator ICOS by D9-tetrahydrocannabinol. J. Leuk. Biol. In press.

Springs, Alison E.B., Karmaus, P.W.F., Crawford, Robert B., Kaplan, Barbara L.F., and Kaminski, Norbert E.  2008.  Effects of targeted deletion of cannabinoid receptors CB1 and CB2 on immune competence and sensitivity to immune modulation by D9-tetrahydrocannabinol. J. Leuk. Biol. In press.

Kaplan, Barbara L.F., Springs, Alison E.B., and Kaminski, Norbert E.  2008. The Profile of Immune Modulation by Cannabidiol (CBD) Involves Deregulation of Nuclear Factor of Activated T Cells (NFAT). Biochem Pharmacol. 76:  726-737.

Rockwell, Cheryl E., Raman, Priyadarshini, Kaplan, Barbara L.F., and Kaminski, Norbert E.  2008.  A COX-2 Metabolite of the Endogenous Cannabinoid, 2-Arachidonyl-Glycerol, Mediates Suppression of IL-2 Secretion in Activated Jurkat T Cells. Biochem. Pharmacol. 76: 353-361.

Kaminski, Norbert E., Faubert Kaplan, Barbara L., and Holsapple, Michael P. 2007. Toxic Responses of the Immune System. In: Casarett and Doull’s Toxicology 7th Edition (ed. C. D. Klaassen). McGraw-Hill, New York.

Kaplan, Barbara L.F., Norell, Hakan, Callender, Glenda G., Ohlum, Tomas, Kiessling, Rolf, and Nishimura, Michael I. 2006.  Interferon-g Renders Tumors that Express Low Levels of Her-2/neu Sensitive to Cytotoxic T Cells. Cancer Immunol. Immunother.  55:653.

Kaplan, Barbara L.F., Ouyang, Yanli, Rockwell, Cheryl, Rao, Gautham, and Kaminski, Norbert E. 2005.  Nuclear Factor of Activated T Cells (NF-AT) and Calcium Signaling are Involved in Suppression of Interferon-g (IFN-g) by the Endogenous Cannabinoid, 2-Arachidonyl-Glycerol. J. Leuk Biol.  77:  966-974.

Kaplan, Barbara L.F., Moore, Tamson V., Schreiber, Karin, Callender, Glenda G., Schreiber, Hans and Nishimura, Michael I. 2005.  A New Murine Model for Studying Human HLA-A2-Restricted Tumor Immunity. Cancer Lett.  224:  153-166.

Kaplan, Barbara L.F., Ouyang, Yanli, Herring, Amy, Yea, Sung Su, Razdan, Raj, and Kaminski, Norbert E.  2004.  Inhibition of Leukocyte Function and Interleukin-2 (IL-2) Gene Expression by 2-Methylarachidonyl-(2'-Fluoroethyl)Amide, a Stable Congener of the Endogenous Cannabinoid Receptor Ligand Anandamide.  2005.  Tox. Applied Pharmacol. 205:  107-115.

Kaplan, Barbara L. F., Yu, David C., Clay, Timothy M. and Nishimura, Michael I. 2003. Redirecting T Lymphocyte Specificity Using T Cell Receptor Genes. Int. Rev. Immunol. 22: 229-253.

Faubert Kaplan, Barbara L. and Kaminski, Norbert E.  2003. Cannabinoids Inhibit the Activation of ERK MAPK in PMA/Io-Stimulated Mouse Splenocytes.  Int. Immunopharmacol.  3: 1503-1510.

Faubert Kaplan, Barbara L, Rockwell, Cheryl E. and Kaminski, Norbert E.  2003. Evidence for Cannabinoid Receptor-Dependent and –Independent Mechanisms of Action in Leukocytes. J. Pharmacol. Exp. Ther.  306:  1077-1085.

Herring, Amy C., Faubert Kaplan, Barbara L. and Kaminski, Norbert E.  2001.  Modulation of CREB and NF-kB Signal Transduction by Cannabinol in Activated Thymocytes. Cell. Signal. 13: 241-250.