Anandamide Concentration-Dependently Modulates Toll-Like Receptor 3 Agonism or UVB-Induced Inflammatory Response of Human Corneal Epithelial Cells

Abstract

Photodamage-induced and viral keratitis could benefit from treatment with novel nonsteroid anti-inflammatory agents. Therefore, we determined whether human corneal epithelial cells (HCECs) express members of the endocannabinoid system (ECS), and examined how the endocannabinoid anandamide (AEA, N-arachidonoyl ethanolamine) influences the Toll-like receptor 3 (TLR3) agonism- or UVB irradiation-induced inflammatory response of these cells. Other than confirming the presence of cannabinoid receptors, we show that endocannabinoid synthesizing and catabolizing enzymes are also expressed in HCECs in vitro, as well as in the epithelial layer of the human cornea in situ, proving that they are one possible source of endocannabinoids. p(I:C) and UVB irradiation was effective in promoting the transcription and secretion of inflammatory cytokines. Surprisingly, when applied alone in 100 nM and 10 μM, AEA also resulted in increased pro-inflammatory cytokine production. Importantly, AEA further increased levels of these cytokines in the UVB model, whereas its lower concentration partially prevented the transcriptional effect of p(I:C), while not decreasing the p(I:C)-induced cytokine release. HCECs express the enzymatic machinery required to produce endocannabinoids both in vitro and in situ. Moreover, our data show that, despite earlier reports about the anti-inflammatory potential of AEA in murine cornea, its effects on the immune phenotype of human corneal epithelium may be more complex and context dependent.

In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties

“…As reported here, CBG and CBD both successfully inhibit C. acnes-TLR-2-induced inflammation in keratinocytes (Figure 2b), suggesting a possible role of cannabinoids in modulating TLR signaling, which is also an emerging dermatological target [31]. This is further supported by reports of CB1 being critical for the innate immune response of TLR-4 [58] and cannabinoids shown to modulate TLR-3 signaling [59]. Thus, while additional research remains to be performed to better characterize the activity of CBG in skin, the early picture suggests that its pleiotropic effects are conferred through both cannabinoid receptors as well as several other receptors in the skin.…”

Sebaceous immunobiology - skin homeostasis, pathophysiology, coordination of innate immunity and inflammatory response and disease associations

“…Thus, one might hypothesize that they can act as regulators of the local cutaneous anti-inflammatory endocannabinoid tone. As mentioned above, cannabinoid signaling can regulate the activity of the immune system, and, in most [but importantly, not all; see ( 208 )] cases, it exerts anti-inflammatory/immunosuppressive effects ( 186 , 187 , 191 , 192 , 209 , 210 ). For example, local endocannabinoid tone was shown to limit mast cell activity in the skin and in other tissues as well via activating CB 1 ( 211 , 212 ).…”