NDLI: Differential Modulation by Delta9-Tetrahydrocannabinol (Δ9-THC) of CD40 Ligand (CD40L) Expression in Activated Mouse Splenic CD4+ T cells

Content Provider	PubMed Central
Author	Ngaotepprutaram, Thitirat Kaplan, Barbara L. F. Crawford, Robert B. Kaminski, Norbert E.
Copyright Year	2012
Abstract	The anti-inflammatory activity of cannabinoids has been widely demonstrated in experimental animal models and in humans. CD40-CD40-ligand (L) interactions are among the most crucial initiators of inflammation. This study investigated the effects of Δ9-THC on CD40L expression in mouse splenic T cells after activation with various stimuli. Time course studies demonstrated that peak surface expression of CD40L by CD4+ T cells after anti-CD3/CD28 or phorbol ester plus calcium ionophore (PMA/Io) occurred 8 h post activation. Peak CD40L mRNA levels were observed at 2 h post PMA/Io treatment and at 4 h post anti-CD3/CD28 treatment. Pretreatment with Δ9-THC significantly impaired the upregulation of CD40L induced by anti-CD3/CD28 at both the protein and mRNA level. By contrast, Δ9-THC did not affect PMA/Io-induced surface CD40L expression on CD4+ T cells. Additionally, Δ9-THC also attenuated anti-CD3/CD28-induced CD40L expression on CD4+ T cells derived from CB1−/−/CB2−/− mice. We investigated whether the mechanism by which Δ9-THC suppressed CD40L expression involved putative cannabinoid activation of the glucocorticoid receptor (GR). Although activation of GR resulted in suppression of CD40L induction by anti-CD3/CD28, no interaction between Δ9-THC and GR was observed by a glucocorticoid response element (GRE) luciferase reporter assay in HEK293T cells. Collectively, these results suggest that Δ9-THC targets proximal T cell receptor-associated signaling in a cannabinoid receptor- and glucocorticoid receptor-independent manner. These findings identify suppression of CD40L expression as a novel part of the mechanism by which Δ9-THC exerts anti-inflammatory activity.
Related Links	http://dx.doi.org/10.1007/s11481-012-9390-z
Ending Page	980
Page Count	12
Starting Page	969
File Format	PDF
ISSN	15571890
e-ISSN	15571904
Journal	Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
Issue Number	4
Volume Number	7
Language	English
Publisher Date	2012-12-01
Access Restriction	Open
Subject Keyword	Immunology Immunology and Allergy Pharmacology Neuroscience (miscellaneous) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Allergy Pharmacology Immunology

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