Δ8-Tetrahydrocannabinol induces cytotoxicity in macrophage J774-1 cells: Involvement of cannabinoid receptor 2 and p38 MAPK

Yamaori, Satoshi; Ishii, Hirosuke; Chiba, Kenzo; Yamamoto, Ikuo; Watanabe, Kazuhito

doi:10.1016/j.tox.2013.10.007

Cited by 16 publications

(7 citation statements)

References 46 publications

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“…Other groups using CB 2 -transfected cell models found signaling events to be PTX-sensitive, supporting the involvement of G i/o proteins [ 85 , 86 ]. This interaction was later confirmed in murine microglial cells [ 87 ], the murine macrophage cell line J774-1 [ 88 ], the human promyelocytic cell line HL-60 [ 89 – 91 ], and human bronchial epithelial cells [ 92 ]. Since it has proven to couple to G i/o proteins, the impact of CB 2 activation on adenylyl cyclase activity was also investigated.…”

Section: Cb 2 Receptor Signalingmentioning

confidence: 96%

The CB2 receptor and its role as a regulator of inflammation

Turcotte

Blanchet

Laviolette

et al. 2016

Cell. Mol. Life Sci.

434

379

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The CB2 receptor is the peripheral receptor for cannabinoids. It is mainly expressed in immune tissues, highlighting the possibility that the endocannabinoid system has an immunomodulatory role. In this respect, the CB2 receptor was shown to modulate immune cell functions, both in cellulo and in animal models of inflammatory diseases. In this regard, numerous studies have reported that mice lacking the CB2 receptor have an exacerbated inflammatory phenotype. This suggests that therapeutic strategies aiming at modulating CB2 signaling could be promising for the treatment of various inflammatory conditions. Herein, we review the pharmacology of the CB2 receptor, its expression pattern, and the signaling pathways induced by its activation. We next examine the regulation of immune cell functions by the CB2 receptor and the evidence obtained from primary human cells, immortalized cell lines, and animal models of inflammation. Finally, we discuss the possible therapies targeting the CB2 receptor and the questions that remain to be addressed to determine whether this receptor could be a potential target to treat inflammatory disease.

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Section: Cb 2 Receptor Signalingmentioning

confidence: 96%

The CB2 receptor and its role as a regulator of inflammation

Turcotte

Blanchet

Laviolette

et al. 2016

Cell. Mol. Life Sci.

434

379

View full text Add to dashboard Cite

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“…p38 MAPK activation by a nonselective CB 2 receptor agonist (D 9 -THC) was found to have a proapoptotic effect in the Jurkat human leukemia cell line (Herrera et al, 2005) and cytotoxicity in J774-1 macrophages (Yamaori et al, 2013). This effect was exclusively mediated by CB 2 receptors (Herrera et al, 2005;Yamaori et al, 2013;Kauppinen et al, 2014).…”

Section: Mapkmentioning

confidence: 99%

“…This effect was exclusively mediated by CB 2 receptors (Herrera et al, 2005;Yamaori et al, 2013;Kauppinen et al, 2014). Interestingly, Yamaori et al (2013), in the same cells, also found a c-Jun N-terminal kinase-mediated cytoprotective effect mediated by D…”

Section: Mapkmentioning

confidence: 99%

CB₂Cannabinoid Receptors as a Therapeutic Target—What Does the Future Hold?

2014

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The past decades have seen an exponential rise in our understanding of the endocannabinoid system, comprising CB 1 and CB 2 cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes that synthesize and degrade endocannabinoids. The primary focus of this review is the CB 2 receptor. CB 2 receptors have been the subject of considerable attention, primarily due to their promising therapeutic potential for treating various pathologies while avoiding the adverse psychotropic effects that can accompany CB 1 receptor-based therapies. With the appreciation that CB 2 -selective ligands show marked functional selectivity, there is a renewed opportunity to explore this promising area of research from both a mechanistic as well as a therapeutic perspective. In this review, we summarize our present knowledge of CB 2 receptor signaling, localization, and regulation. We discuss the availability of genetic tools (and their limitations) to study CB 2 receptors and also provide an update on preclinical data on CB 2 agonists in pain models. Finally, we suggest possible reasons for the failure of CB 2 ligands in clinical pain trials and offer possible ways to move the field forward in a way that can help reconcile the inconsistencies between preclinical and clinical data.

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“…A quantitative real-time polymerase chain reaction (qPCR) was performed using an ABI 7500 realtime PCR system (Applied Biosystems) with the KAPA SYBR ® Fast qPCR Kit (Nippon Genetics, Tokyo, Japan) according to the manufacturer's instructions. Primers used for mRNA measurements of Cyp1a1, Cyp1a2, Cyp1b1 (Uno et al, 2008), Cyp2a5 (Arpiainen et al, 2008), Cyp2b10 (Koike et al, 2007), Cyp3a11 (van den Bosch et al, 2007), CB1R, CB2R, and β-actin (Yamaori et al, 2013) were described previously. The other primers (Cyp2b9, Cyp2b13, Cyp2b19, Cyp2c29, Cyp2c37, Cyp2c38, Cyp2c39, Cyp2c40, Cyp2c44, Cyp2c50, Cyp2c55, Cyp2d9, Cyp2d10, Cuyp2d12, Cyp2d22, Cyp2d26, Cyp2d34, Cyp2e1, Cyp3a13, Cyp3a16, Cyp3a25, Cyp3a41, Cyp3a44, Cyp4a10, Cyp4a12, Cyp4a14, Cyp4f13, Cyp4f14, Cyp4f15, Cyp4f16, Cyp4f18, Cyp4x1, and Cyp46a1) were designed using qPrimerDepot (http://mouseprimerdepot.nci.nih.gov).…”

Section: Rna Analysismentioning

confidence: 99%

Expression levels of 39 Cyp mRNAs in the mouse brain and neuroblastoma cell lines, C-1300N18 and NB2a – strong expression of Cyp1b1

Yamaori

Jiang

Maeda

et al. 2017

Fundam. Toxicol. Sci.

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-An analysis of mRNA levels of 39 Cyp enzymes in the mouse brain and neuroblastoma cell lines, C-1300N18 and NB2a was performed using a real-time reverse transcriptase-polymerase chain reaction. Relative expression levels were quantified by normalized β-actin levels, and compared to the mRNA expression level of the cannabinoid receptor (CB1R), which is abundantly expressed in the mouse brain. Mean 2^-ddCts of CB1R in mouse brain, C-1300N18, and NB2a cells were 1.043, 1.003, and 1.005, respectively. Among Cyp mRNAs in the mouse brain, Cyp1b1 mRNA was the most abundantly expressed (2^-ddCt = 0.310), followed by Cyp46a1 mRNA (0.246). The other Cyp mRNAs moderately expressed (0.011 ~ 0.117) were Cyp1a1, 1a2, 2b10, 2c29, 2c50, 2d9, 2d10, 2d12, 2d22, 2d26, 3a11, 3a41, 4f14, 4f15, 4f16, and 4x1. On the other hand, 10 out of 39 Cyp mRNAs (Cyp 2b9, 2b13, 2b19, 2c37, 2c38, 2c55, 3a44, 4a12, 4a14, and 4f18) were not detectable (2^-ddCt < 0.001). In the neuroblastoma cell lines, C-1300N18 and NB2a, Cyp1b1 mRNA was also the most abundant and preferentially expressed, and relative expression levels to CB1R were 4.674 and 5.084, respectively. Thirteen other Cyp mRNAs (Cyp1a1, 1a2, 2a5, 2b10, 2c44, 2c50, 2c55, 2d10, 2d22, 3a11, 4f13, 4f15, and 4f16) were detected in the neuroblastoma cell lines, whereas 17 Cyp mRNAs (Cyp2c29, 2c37, 2c39, 2c40, 2d12, 2d34, 2e1, 3a16, 3a25, 3a41, 3a44, 4a10, 4a12, 4a14, 4f14, 4x1, and 46a1) were not under the current conditions. The pattern of Cyp mRNA expression was similar for both neuroblastoma cell lines. The present results provide fundamental and useful information on the significance of particular Cyp enzymes in the mouse brain and neuroblastoma cell lines, C-1300N18 and NB2a, which may be valuable tools for investigations on the neural expression and function of Cyp1b1.

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Δ8-Tetrahydrocannabinol induces cytotoxicity in macrophage J774-1 cells: Involvement of cannabinoid receptor 2 and p38 MAPK

Cited by 16 publications

References 46 publications

The CB2 receptor and its role as a regulator of inflammation

The CB2 receptor and its role as a regulator of inflammation

CB₂Cannabinoid Receptors as a Therapeutic Target—What Does the Future Hold?

Expression levels of 39 Cyp mRNAs in the mouse brain and neuroblastoma cell lines, C-1300N18 and NB2a – strong expression of Cyp1b1

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Δ8-Tetrahydrocannabinol induces cytotoxicity in macrophage J774-1 cells: Involvement of cannabinoid receptor 2 and p38 MAPK

Cited by 16 publications

References 46 publications

The CB2 receptor and its role as a regulator of inflammation

The CB2 receptor and its role as a regulator of inflammation

CB2Cannabinoid Receptors as a Therapeutic Target—What Does the Future Hold?

Expression levels of 39 Cyp mRNAs in the mouse brain and neuroblastoma cell lines, C-1300N18 and NB2a – strong expression of Cyp1b1

Contact Info

Product

Resources

About

CB₂Cannabinoid Receptors as a Therapeutic Target—What Does the Future Hold?