A Cannabinoid CB2 Receptor Agonist Attenuates Experimental Autoimmune

Thread starter #1
A Cannabinoid CB2 receptor agonist attenuates experimental autoimmune encephalomyelitis (EAE) and reduces MOG-specific T cell proliferation

Ming Zhang1, Jui-Hung Yen1,2, Tanzilya Kharullina1,2, Doina Ganea1 and Ronald F Tuma1

1 Physiology, Temple University, 3420 N Broad Street, Philadelphia, PA, 19027,
2 Biological Science, Rutgers University, 101 Warren Street, Newark, NJ, 07102

ABSTRACT

Inflammatory responses caused by antigen presenting cell (APC) and T lymphocytes play an important role in initiation and progress of Multiple Sclerosis (MS). The cannabinoid CB2 receptor is primarily expressed by cells of the immune system and CB2 receptor activation has been show to down-regulate immune responses. The purpose of this investigation was to determine if a selective CB2 agonist interferes with splenic T cell proliferation and attenuates the progress of EAE. EAE was induced with murine myelin oligodendrocyte protein (MOG) (day 0) and pertussis toxin (day 0 and +2) in C57BL/6 mice. Vehicle or CB2 agonist (1 mg/kg) was given on day 7 and every four days afterwards (total of six administrations) for clinical EAE; and on days 5 and 9 for splenocytes proliferation. Motor function was examined daily from day 7 to day 28. Splenocytes were harvested at day 11 and cultured in the presence or absence of MOG or {alpha}-CD3 Abs for 4 days. Proliferation was measured by BrdU incorporation. The results demonstrate that the CB2 agonist slowed down the neurological deficits in EAE, and attenuated splenocyte proliferation in response to MOG, but not anti-CD3 Abs, as compared to vehicle treated animals. We concluded that CB2 activation attenuates EAE partially by inhibiting T lymphocyte proliferation in response to the specific antigen.

This project is funded, in part, under a grant with the Pennsylvania Department of Health.


Source: A Cannabinoid CB2 receptor agonist attenuates experimental autoimmune encephalomyelitis (EAE) and reduces MOG-specific T cell proliferation