Targeting Cutaneous Cannabinoid Signaling in Inflammation - A “High”-way to Heal?

Oláh, Attila; Bı́ró, Tamás

doi:10.1016/j.ebiom.2017.01.003

Cited by 26 publications

(25 citation statements)

References 9 publications

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“…(Kovács et al, 2016;Tó th et al, 2011;Zouboulis et al, 2008Zouboulis et al, , 2014. Furthermore, we have previously shown that, besides the aforementioned regulators, human SGs are also important players in the endocannabinoid system (ECS) of the skin (Dobrosi et al, 2008;Oláh and Bíró , 2017).…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoid Tone Regulates Human Sebocyte Biology

Zákány

Oláh

Markovics

et al. 2018

Journal of Investigative Dermatology

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We have previously shown that endocannabinoids (eCBs) (e.g., anandamide) are involved in the maintenance of homeostatic sebaceous lipid production in human sebaceous glands and that eCB treatment dramatically increases sebaceous lipid production. Here, we aimed to investigate the expression of the major eCB synthesizing and degrading enzymes and to study the effects of eCB uptake inhibitors on human SZ95 sebocytes, thus exploring the role of the putative eCB membrane transporter, which has been hypothesized to facilitate the cellular uptake and subsequent degradation of eCBs. We found that the major eCB synthesizing (N-acyl phosphatidylethanolamine-specific phospholipase D, and diacylglycerol lipase-α and -β) and degrading (fatty acid amide hydrolase, monoacylglycerol lipase) enzymes are expressed in SZ95 sebocytes and also in sebaceous glands (except for diacylglycerol lipase-α, the staining of which was dubious in histological preparations). eCB uptake-inhibition with VDM11 induced a moderate increase in sebaceous lipid production and also elevated the levels of various eCBs and related acylethanolamides. Finally, we found that VDM11 was able to interfere with the proinflammatory action of the TLR4 activator lipopolysaccharide. Collectively, our data suggest that inhibition of eCB uptake exerts anti-inflammatory actions and elevates both sebaceous lipid production and eCB levels; thus, these inhibitors might be beneficial in cutaneous inflammatory conditions accompanied by dry skin.

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Section: Introductionmentioning

confidence: 99%

Endocannabinoid Tone Regulates Human Sebocyte Biology

Zákány

Oláh

Markovics

et al. 2018

Journal of Investigative Dermatology

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“…These processes are part of the repair mechanism for the skin barrier after experimental disruption as well as in acute contact dermatitis . The known anti‐inflammatory effects of ECs seem to be of special importance . In keratinocytes, FAAH was upregulated following treatment with inflammatory stimuli .…”

Section: Discussionmentioning

confidence: 99%

“…The latter two compounds are thought to activate both CB receptors in keratinocytes by elevating extracellular AEA concentration. Moreover, FAAH inhibition by WOBE440 will increase intracellular AEA concentration as a first step and at the same time decrease the concentration of the pro‐inflammatory AEA degradation product arachidonic acid (AA) in the cell . Since the molecular target of WOL067‐531 has not been identified to date, the compound might interfere with intracellular endocannabinoid signalling as well.…”

Section: Introductionmentioning

confidence: 99%

Modulators of the endocannabinoid system influence skin barrier repair, epidermal proliferation, differentiation and inflammation in a mouse model

Proksch

Soeberdt

Kilić

et al. 2019

Experimental Dermatology

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Endocannabinoids (ECs) are important regulators of cell signalling. Cannabinoid receptors are involved in keratinocyte proliferation/differentiation. Elevation of the endogenous cannabinoid tone leads to strong anti‐inflammatory effects. Here, we explored the influence of endocannabinoid system (ECS) modulators on skin permeability barrier repair, epidermal proliferation, differentiation and inflammation in hairless mice. We used WOBE440, a selective fatty acid amide hydrolase (FAAH) inhibitor, WOL067‐531, an inhibitor of endocannabinoid reuptake with no relevant FAAH activity, which both signal via cannabinoid receptor‐1 and cannabinoid receptor‐2 (CB‐1R and CB‐2R) and compared them to WOBE15 which signals via CB‐2R. Barrier disruption and skin irritation were induced by tape stripping or by sodium dodecyl sulphate (SDS) patch testing. Immediately after barrier disruption, 30 μL of 0.5% WOBE440, WOL067‐531 and WOBE15 solutions or the vehicle was applied topically. Barrier repair was monitored by transepidermal water loss at 1.5, 3, 5 and 7 hours. We found that barrier repair was significantly delayed by WOL067‐531. A tendency for a delay was noticed for WOBE440, whereas for WOBE15, no effect was observed. Immunohistology showed that the tape‐stripping‐induced increase in epidermal proliferation and filaggrin expression was significantly reduced by topical applications of WOL067‐531 and WOBE440, but not by WOBE15. Also, the SDS‐induced inflammation, as determined by the number of inflammatory cells, was reduced by WOL067‐531 and WOBE440. In summary, we showed that WOL067‐531 exhibits a significant effect on skin barrier repair, epidermal proliferation/differentiation and inflammation.

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“…25 The endocannabinoid system consists of at least 2 receptors coupled through G-protein inhibition: cannabinoid receptor 1 (CB 1 ) and cannabinoid receptor 2 (CB 2 ). [26][27][28][29][30] Other receptors sensitive to cannabinoids include vanilloid receptor 1 (TRPV1), 31,32 adenosine receptors, 33,34 5-hydroxytryptamine (5-HT 1A ), 35,36 and G-protein coupled receptors. 37 The CB 1 receptors are most abundant within the central nervous system, located primarily on the axon and synaptic terminals on the neurons, 38 while the CB 2 receptors are much more concentrated within the peripheral nervous system, such as the immune system.…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Neuroprotection Following Concussion: The Potential Role for Cannabidiol

Singh

Neary

2020

Can. J. Neurol. Sci.

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ABSTRACT:Cannabidiol (CBD) has been generating increasing interest in medicine due to its therapeutic properties and an apparent lack of negative side effects. Research has suggested that high dosages of CBD can be taken acutely and chronically with little to no risk. This review focuses on the neuroprotective effects of a CBD, with an emphasis on its implications for recovering from a mild traumatic brain injury (TBI) or concussion. CBD has been shown to influence the endocannabinoid system, both by affecting cannabinoid receptors and other receptors involved in the endocannabinoid system such as vanilloid receptor 1, adenosine receptors, and 5-hydroxytryptamine via cannabinoid receptor-independent mechanisms. Concussions can result in many physiological consequences, potentially resulting in post-concussion syndrome. While impairments in cerebrovascular and cardiovascular physiology following concussion have been shown, there is unfortunately still no single treatment available to enhance recovery. CBD has been shown to influence the blood brain barrier, brain-derived neurotrophic factors, cognitive capacity, the cerebrovasculature, cardiovascular physiology, and neurogenesis, all of which have been shown to be altered by concussion. CBD can therefore potentially provide treatment to enhance neuroprotection by reducing inflammation, regulating cerebral blood flow, enhancing neurogenesis, and protecting the brain against reactive oxygen species. Double-blind randomized controlled trials are still required to validate the use of CBD as medication following mild TBIs, such as concussion.

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Targeting Cutaneous Cannabinoid Signaling in Inflammation - A “High”-way to Heal?

Cited by 26 publications

References 9 publications

Endocannabinoid Tone Regulates Human Sebocyte Biology

Endocannabinoid Tone Regulates Human Sebocyte Biology

Modulators of the endocannabinoid system influence skin barrier repair, epidermal proliferation, differentiation and inflammation in a mouse model

Neuroprotection Following Concussion: The Potential Role for Cannabidiol

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