Anandamide inhibits FcεRI-dependent degranulation and cytokine synthesis in mast cells through CB2 and GPR55 receptor activation. Possible involvement of CB2-GPR55 heteromers

Cruz, Silvia L.; Sánchez-Miranda, Elizabeth; Castillo-Arellano, Jorge Iván; Cervantes‐Villagrana, Rodolfo Daniel; Ibarra-Sánchez, Alfredo; González-Espinosa, Claudia

doi:10.1016/j.intimp.2018.09.006

Cited by 34 publications

(24 citation statements)

References 69 publications

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“…GPCRs such as CB2 and GPR55 activated by anandamide and specific agonists inhibit mast cell degranulation. 219 Tumors are innervated by sensorial fibers, in papillary thyroid cancer are detected peptidergic (sensorial fibers) and cholinergic (parasympathetic fibers) innervations, although most nerves are commonly adrenergic (sympathetic fibers). 208 Direct communication between sensorial afferent fibers and cancer cells stimulates proliferation and invasion of transformed cells.…”

Section: Sema4f Knock Downmentioning

confidence: 99%

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Cervantes‐Villagrana

Albores-García

Cervantes-Villagrana

et al. 2020

Sig Transduct Target Ther

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147

112

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Normal cells are hijacked by cancer cells forming together heterogeneous tumor masses immersed in aberrant communication circuits that facilitate tumor growth and dissemination. Besides the well characterized angiogenic effect of some tumor-derived factors; others, such as BDNF, recruit peripheral nerves and leukocytes. The neurogenic switch, activated by tumor-derived neurotrophins and extracellular vesicles, attracts adjacent peripheral fibers (autonomic/sensorial) and neural progenitor cells. Strikingly, tumor-associated nerve fibers can guide cancer cell dissemination. Moreover, IL-1β, CCL2, PGE 2 , among other chemotactic factors, attract natural immunosuppressive cells, including T regulatory (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages, to the tumor microenvironment. These leukocytes further exacerbate the aberrant communication circuit releasing factors with neurogenic effect. Furthermore, cancer cells directly evade immune surveillance and the antitumoral actions of natural killer cells by activating immunosuppressive mechanisms elicited by heterophilic complexes, joining cancer and immune cells, formed by PD-L1/PD1 and CD80/CTLA-4 plasma membrane proteins. Altogether, nervous and immune cells, together with fibroblasts, endothelial, and bone-marrow-derived cells, promote tumor growth and enhance the metastatic properties of cancer cells. Inspired by the demonstrated, but restricted, power of anti-angiogenic and immune cell-based therapies, preclinical studies are focusing on strategies aimed to inhibit tumor-induced neurogenesis. Here we discuss the potential of anti-neurogenesis and, considering the interplay between nervous and immune systems, we also focus on anti-immunosuppression-based therapies. Small molecules, antibodies and immune cells are being considered as therapeutic agents, aimed to prevent cancer cell communication with neurons and leukocytes, targeting chemotactic and neurotransmitter signaling pathways linked to perineural invasion and metastasis.

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Section: Sema4f Knock Downmentioning

confidence: 99%

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Cervantes‐Villagrana

Albores-García

Cervantes-Villagrana

et al. 2020

Sig Transduct Target Ther

Self Cite

147

112

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“…Additionally, GPR55 seems to be a promising target. AEA was shown to inhibit mast cells degranulation in vitro via CB2 and GPR55 activation, and CB2-GPR55 heterodimers were probably involved [208]. On the other hand, GPR55 antagonists exhibited anti-neuroinflammatory action in vitro [170].…”

Section: Inflammatory and Autoimmune Diseasesmentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.

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“…In contrast to the above data, 30 μM WIN55,212-2 was found to CB 2 -dependently prevent degranulation of LAD2 cells induced by the supernatant of human HPV18-positive SW756 cervical carcinoma cells [240]. Moreover, AEA inhibited FcεRI-dependent degranulation and cytokine synthesis in murine bone marrow-derived MCs via the activation of CB 2 /GPR55 receptor heteromers [241], and VCE-004.3, as well as VCE-004.8, two PPARγ and CB 2 receptor activating derivatives of CBD, could also reduce MC degranulation in bleomycin-induced murine fibrosis [242,243].…”

Section: Translational Potential Of the Cutaneous Cannabinoid Signmentioning

confidence: 99%

Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System

et al. 2019

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The endocannabinoid system (ECS) has lately been proven to be an important, multifaceted homeostatic regulator, which influences a wide-variety of physiological processes all over the body. Its members, the endocannabinoids (eCBs; e.g., anandamide), the eCB-responsive receptors (e.g., CB1, CB2), as well as the complex enzyme and transporter apparatus involved in the metabolism of the ligands were shown to be expressed in several tissues, including the skin. Although the best studied functions over the ECS are related to the central nervous system and to immune processes, experimental efforts over the last two decades have unambiguously confirmed that cutaneous cannabinoid (“c[ut]annabinoid”) signaling is deeply involved in the maintenance of skin homeostasis, barrier formation and regeneration, and its dysregulation was implicated to contribute to several highly prevalent diseases and disorders, e.g., atopic dermatitis, psoriasis, scleroderma, acne, hair growth and pigmentation disorders, keratin diseases, various tumors, and itch. The current review aims to give an overview of the available skin-relevant endo- and phytocannabinoid literature with a special emphasis on the putative translational potential, and to highlight promising future research directions as well as existing challenges.

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Anandamide inhibits FcεRI-dependent degranulation and cytokine synthesis in mast cells through CB2 and GPR55 receptor activation. Possible involvement of CB2-GPR55 heteromers

Cited by 34 publications

References 69 publications

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

A Guide to Targeting the Endocannabinoid System in Drug Design

Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System

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