Cannabinoid receptors and T helper cells

Klein, Thomas; Newton, Cathy; Larsen, Kellie; Chou, Joe C.; Perkins, Izabella; Lu, Lily; Nong, Liang; Friedman, Herman

doi:10.1016/j.jneuroim.2003.10.019

Cited by 82 publications

(64 citation statements)

References 20 publications

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“…Further, they play important role in endotoxic shock and inflammation. 14 The level of AEA in brain was reported to be 35 plus or minus 8 pmol/g, and 2-AG levels were in brain was reported to be 62 plus or minus 1.8 nmol/g compared with the expression in blood of AEA (2.5 Ϯ 0.7 pmol/g) and 2-AG (10 Ϫ3 nmol/g). 33 Here, we report that 2-AG and AEA are found in similar levels to those reported in brain.…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization

Jiang

Alberich-Jordà

Zagożdżon

et al. 2011

Blood

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Endocannabinoids are arachidonic acid derivatives and part of a novel bioactive lipid signaling system, along with their G-coupled cannabinoid receptors (CB 1 and CB 2 ) and the enzymes involved in their biosynthesis and degradation. However, their roles in hematopoiesis and hematopoietic stem and progenitor cell (HSPC) functions are not well characterized. Here, we show that bone marrow stromal cells express endocannabinoids (anandamide and 2-arachidonylglycerol), whereas CB 2 receptors are expressed in human and murine HSPCs. On ligand stimulation with CB 2 agonists, CB 2 receptors induced chemotaxis, migration, and enhanced colony formation of bone marrow cells, which were mediated via ERK, PI3-kinase, and G␣i-Rac1 pathways. In vivo, the CB 2 agonist AM1241 induced mobilization of murine HSPCs with shortand long-term repopulating abilities. In addition, granulocyte colony-stimulating factor -induced mobilization of HSPCs was significantly decreased by specific CB 2 antagonists and was impaired in Cnr2 ؊/؊ cannabinoid type 2 receptor knockout mice. Taken together, these results demonstrate that the endocannabinoid system is involved in hematopoiesis and that CB 2 /CB 2 agonist axis mediates repopulation of hematopoiesis and mobilization of HSPCs. Thus, CB 2 agonists may be therapeutically applied in clinical conditions, such as bone marrow transplantation. (Blood. 2011;117(3):827-838) IntroductionEndocannabinoids and exogenous cannabinoid ligands bind to and activate the cannabinoid receptors CB 1 and CB 2 . 1-3 Endocannabinoids are endogenous lipid mediators generated by many cell types both in the brain and peripheral tissues, which exert a broad range of biologic effects, such as cardiovascular, neurologic, and antiinflammatory effects. 4 Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the 2 most widely studied endocannabinoids. The endocannabinoid system represents a pivotal neuroprotective mechanism both in acute forms of neuronal injury (such as stroke and traumatic brain injury) and chronic neurodegenerative disorders. [4][5][6][7][8] The synthetic and natural ligands of cannabinoid receptors exert various anti-inflammatory and neuroprotective effects by several mechanisms that include inhibiting the generation and release of proinflammatory cytokines, activation of cytoprotective signaling pathways, modulation of calcium homeostasis, and excitability via interactions with Ca ϩ2 , K ϩ , and Na ϩ channels as well as antioxidant properties of endocannabinoids. [4][5][6][7][8] Both the CB 1 and CB 2 receptors are 7-transmembrane G␣/i protein-coupled receptors (GPCRs) and are highly conserved during evolution. 2,9 The CB 2 receptor is predominantly expressed in the immune system, such as B and T cells, natural killer cells, monocytes, and neutrophils, where cannabinoids can modulate cytokine release and immune cell migration. Although the expression and function of cannabinoid receptors in mature hematologic and immune cells were reported, 9-14 the effect of cannabinoids on hematopoietic stem and pro...

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Section: Discussionmentioning

confidence: 99%

Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization

Jiang

Alberich-Jordà

Zagożdżon

et al. 2011

Blood

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“…tors in mature hematopoietic and immune cells (21)(22)(23), whereas the effect of cannabinoids on HSPCs has not been investigated in depth. Noteworthy, endocannabinoids promoted the growth of primary murine marrow progenitor cells (24).…”

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confidence: 99%

Endocannabinoids Are Expressed in Bone Marrow Stromal Niches and Play a Role in Interactions of Hematopoietic Stem and Progenitor Cells with the Bone Marrow Microenvironment

Jiang

Zagożdżon

Alberich-Jordà

et al. 2010

Journal of Biological Chemistry

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“…CB2Rs were originally thought essentially to be confined to immune system cells and to be absent from brain tissues (36). Thus CB2R has been demonstrated to reside on a wide variety of peripheral blood leukocytes and spleen cell populations (26) and to a greater extent than seen for CB1R in the same cell types that include B cells, T cells, NK cells, splenic macrophages, dendritic cells, and neutrophils (5,25,30). More recently, the existence of a CB2R on peripheral neurons (15) and perivascular microglial cells (37) in human brain has been reported.…”

Section: Discussionmentioning

confidence: 99%

Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium

Kimball

Schneider²,

Wallace³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

161

168

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of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium. Am J Physiol Gastrointest Liver Physiol 291: G364 -G371, 2006. First published March 30, 2006 doi:10.1152/ajpgi.00407.2005.-Oil of mustard (OM) is a potent neuronal activator that is known to elicit visceral hyperalgesia when given intracolonically, but the full extent to which OM is also proinflammatory in the gastrointestinal tract is not known. We have previously shown that male CD-1 mice given a single administration of 0.5% OM develop a severe colitis that is maximum at day 3 and that gradually lessens until essentially absent by day 14. OM-induced neuronal stimulation is reported to be reduced by cannabinoid agonists, and cannabinoid receptor 1 (CB1R) Ϫ/Ϫ mice have exacerbated experimental colitis. Therefore, we examined the role of cannabinoids in this OM-induced 3-day model of colitis in CD-1 mice and in a 7-day dextran sulfate sodium (DSS) colitis model in BALB/c mice. In OM colitis, the CB1R-selective agonist ACEA and the CB2R-selective agonist JWH-133 reduced (P Ͻ 0.05) colon weight gain (means Ϯ SE; 82 Ϯ 13% and 47 Ϯ 15% inhibition, respectively), colon shrinkage (98 Ϯ 24% and 42 Ϯ 12%, respectively), colon inflammatory damage score (49 Ϯ 11% and 40 Ϯ 12%, respectively), and diarrhea (58 Ϯ 12% and 43 Ϯ 11%, respectively). Histological damage was similarly reduced by these treatments. Likewise, CBR agonists attenuated DSS colitis, albeit at higher doses; ACEA at 10 mg/kg, twice daily, inhibited (P Ͻ 0.05) macroscopic and microscopic scores (46 Ϯ 9% and 63 Ϯ 7%, respectively); whereas 20 mg/kg, twice daily, of JWH-133 was required to diminish (P Ͻ 0.05) macroscopic and microscopic scores (29 Ϯ 7% and 43 Ϯ 5%, respectively). CB1R and CB2R immunostaining of colon sections revealed that CB1R in enteric neurons was more intense in colitic vs. control mice; however, CB1R was also increased in the endothelial layer in OM colitis only. CB2R immunostaining was more marked in infiltrated immune cells in OM colitis. These findings validate the OM colitis model with respect to the DSS model and provide strong support to the emerging idea that cannabinoid receptor activation mediates protective mechanisms in experimental colitis. The demonstration of CB1R agonist effects in colitis support the neurogenic nature of the OM-induced colitis model and reinforce the importance of neuronal activation in intestinal inflammation.

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Cannabinoid receptors and T helper cells

Cited by 82 publications

References 20 publications

Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization

Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization

Endocannabinoids Are Expressed in Bone Marrow Stromal Niches and Play a Role in Interactions of Hematopoietic Stem and Progenitor Cells with the Bone Marrow Microenvironment

Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium

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