CB(1) and CB(2) cannabinoid receptors mediate different aspects of delta-9-tetrahydrocannabinol (THC)-induced T helper cell shift following immune activation by Legionella pneumophila infection

Autor: Thomas W. Klein, Catherine Newton, Ping-Jen Chou, Izabella Perkins
Rok vydání: 2008
Předmět:
medicine.medical_specialty
Cannabinoid receptor
medicine.medical_treatment
Immunology
Neuroscience (miscellaneous)
Enzyme-Linked Immunosorbent Assay
GATA3 Transcription Factor
Biology
Proinflammatory cytokine
Receptor
Cannabinoid
CB2
Mice
Th2 Cells
Receptor
Cannabinoid
CB1
Internal medicine
mental disorders
medicine
Cannabinoid receptor type 2
Immunology and Allergy
Animals
Serrate-Jagged Proteins
Dronabinol
Interleukin-12 Receptor beta 2 Subunit
Receptor
Transcription factor
Pharmacology
Mice
Knockout
Immunity
Cellular
Mice
Inbred BALB C
Reverse Transcriptase Polymerase Chain Reaction
Calcium-Binding Proteins
Transcription Factor RelA
Membrane Proteins
T helper cell
Dendritic Cells
T-Lymphocytes
Helper-Inducer
Macrophage Activation
Endocrinology
medicine.anatomical_structure
Hallucinogens
Cannabinoid receptor antagonist
Intercellular Signaling Peptides and Proteins
lipids (amino acids
peptides
and proteins)
Female
Cannabinoid
Legionnaires' Disease
Jagged-1 Protein
Spleen
Zdroj: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 4(1)
ISSN: 1557-1904
Popis: Legionella pneumophila infection of mice induces proinflammatory cytokines and Th1 immunity as well as rapid increases in serum levels of IL-12 and IFNgamma and splenic IL-12Rbeta2 expression. Delta-9-tetrahydrocannabinol (THC) treatment prior to infection causes a shift from Th1 to Th2 immunity and here we demonstrate that CB(1) and CB(2) cannabinoid receptors mediate different aspects of the shift. Using cannabinoid receptor antagonists and cannabinoid receptor gene deficient mice (CB(1) (-/-) and CB(2) (-/-)), we showed that both CB(1) and CB(2) receptors were involved in the THC-induced attenuation of serum IL-12 and IFNgamma. IFNgamma production is dependent upon signaling through IL-12Rbeta2 (beta2) and THC treatment suppressed splenic beta2 message; moreover, this effect was CB(1) but not CB(2)-dependent from studies with receptor antagonists and CB1(-/-) and CB2(-/-) mice. Furthermore, observed increases in IL-4 induced by THC, were not involved in the drug effect on beta2 from studies with IL-4 deficient mice. The GATA-3 transcription factor is necessary for IL-4 production and is selectively expressed in Th2 cells. GATA-3 message levels were elevated in spleens of THC-treated and L. pneumophila-infected mice and the effect was shown to be CB(2) but not CB(1)-dependent. Furthermore, GATA-3 regulatory factors were modulated in that Notch ligand Delta4 mRNA was decreased and Jagged1 increased by THC also in a CB2-dependent manner and splenic NFkappaB p65 was increased. Together, these results indicate that CB(1) and CB(2) mediate the THC-induced shift in T helper activity in L. pneumophila-infected mice, with CB(1) involved in suppressing IL-12Rbeta2 and CB(2) involved in enhancing GATA-3.
Databáze: OpenAIRE
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