scholarly journals N-Palmitoyl Serinol Stimulates Ceramide Production through a CB1-Dependent Mechanism in In Vitro Model of Skin Inflammation

2021 ◽  
Vol 22 (15) ◽  
pp. 8302
Author(s):  
Kyong-Oh Shin ◽  
Sungeun Kim ◽  
Byeong Deog Park ◽  
Yoshikazu Uchida ◽  
Kyungho Park
Keyword(s):  
Barrier Function ◽  
In Vitro Model ◽  
Skin Inflammation ◽  
Permeability Barrier ◽  
Epidermal Permeability Barrier ◽  
Vitro Model ◽  
Endocannabinoid Receptor ◽  
Long Chain ◽  
Dependent Mechanism

Ceramides, a class of sphingolipids containing a backbone of sphingoid base, are the most important and effective structural component for the formation of the epidermal permeability barrier. While ceramides comprise approximately 50% of the epidermal lipid content by mass, the content is substantially decreased in certain inflammatory skin diseases, such as atopic dermatitis (AD), causing improper barrier function. It is widely accepted that the endocannabinoid system (ECS) can modulate a number of biological responses in the central nerve system, prior studies revealed that activation of endocannabinoid receptor CB1, a key component of ECS, triggers the generation of ceramides that mediate neuronal cell fate. However, as the impact of ECS on the production of epidermal ceramide has not been studied, we here investigated whether the ECS stimulates the generation of epidermal ceramides in an IL-4-treated in vitro model of skin inflammation using N-palmitoyl serinol (PS), an analog of the endocannabinoid N-palmitoyl ethanolamine. Accordingly, an IL-4-mediated decrease in cellular ceramide levels was significantly stimulated in human epidermal keratinocytes (KC) following PS treatment through both de novo ceramide synthesis- and sphingomyelin hydrolysis-pathways. Importantly, PS selectively increases ceramides with long-chain fatty acids (FAs) (C22–C24), which mainly account for the formation of the epidermal barrier, through activation of ceramide synthase (CerS) 2 and Cer3 in IL-4-mediated inflamed KC. Furthermore, blockade of cannabinoid receptor CB1 activation by AM-251 failed to stimulate the production of total ceramide as well as long-chain ceramides in response to PS. These studies demonstrate that an analog of endocannabinoid, PS, stimulates the generation of specific ceramide species as well as the total amount of ceramides via the endocannabinoid receptor CB1-dependent mechanism, thereby resulting in the enhancement of epidermal permeability barrier function.

Effect of Fecal Water on an In Vitro Model of Colonic Mucosal Barrier Function

2007 ◽  
Vol 57 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Chris I. R. Gill ◽  
Patricia Heavey ◽  
Eileen McConville ◽  
Ian Bradbury ◽  
Caroline Fässler ◽  
...  
Keyword(s):  
Barrier Function ◽  
In Vitro Model ◽  
Mucosal Barrier ◽  
Mucosal Barrier Function ◽  
Fecal Water ◽  
Vitro Model

scholarly journals Cell model of inflammation

2008 ◽  
Vol 28 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Jocelyne Franchi ◽  
Clarisse Marteau ◽  
Claire Crola Da Silva ◽  
Michèle Mitterrand ◽  
Patrice André ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Cell Model ◽  
Cell Communication ◽  
Skin Inflammation ◽  
Selective Reaction ◽  
Vitro Model ◽  
Conditioned Culture Medium ◽  
Inflammatory Molecules ◽  
Leucocyte Recruitment

Chemical and physical stimuli trigger a cutaneous response by first inducing the main epidermal cells, keratinocytes, to produce specific mediators that are responsible for the initiation of skin inflammation. Activation modulates cell communication, namely leucocyte recruitment and blood-to-skin extravasation through the selective barrier of the vascular ECs (endothelial cells). In the present study, we describe an in vitro model which takes into account the various steps of human skin inflammation, from keratinocyte activation to the adhesion of leucocytes to dermal capillary ECs. Human adult keratinocytes were subjected to stress by exposure to UV irradiation or neuropeptides, then the conditioned culture medium was used to mimic the natural micro-environmental conditions for dermal ECs. A relevant in vitro model must include appropriate cells from the skin. This is shown in the present study by the selective reaction of dermal ECs compared with EC lines from distinct origins, in terms of leucocyte recruitment, sensitivity to stress and nature of the stress-induced secreted mediators. This simplified model is suitable for the screening of anti-inflammatory molecules whose activity requires the presence of various skin cells.

scholarly journals The insulin-sensitizing mechanism of myo-inositol is associated with AMPK activation and GLUT-4 expression in human endometrial cells exposed to a PCOS environment

2020 ◽  
Vol 318 (2) ◽  
pp. E237-E248 ◽  
Author(s):  
Heidy Cabrera-Cruz ◽  
Lorena Oróstica ◽  
Francisca Plaza-Parrochia ◽  
Ignacio Torres-Pinto ◽  
Carmen Romero ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
In Vitro Model ◽  
Normal Weight ◽  
Endometrial Cells ◽  
Insulin Resistant ◽  
Protein Levels ◽  
Glut 4 ◽  
Vitro Model ◽  
Dependent Mechanism

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by hyperandrogenism and ovulatory dysfunction but also obesity and hyperinsulinemia. These characteristics induce an insulin-resistant state in tissues such as the endometrium, affecting its reproductive functions. Myo-inositol (MYO) is an insulin-sensitizing compound used in PCOS patients; however, its insulin-sensitizing mechanism is unclear. To understand the relationship of MYO with insulin action in endometrial cells, sodium/myo-inositol transporter 1 (SMIT-1) (MYO-transporter), and MYO effects on protein levels related to the insulin pathway were evaluated. SMIT-1 was assessed in endometrial tissue from women with normal weight, obesity, insulin resistance, and PCOS; additionally, using an in vitro model of human endometrial cells exposed to an environment resembling hyperinsulinemic-obese-PCOS, MYO effect was evaluated on p-AMPK and GLUT-4 levels and glucose uptake by Western blot, immunocytochemistry, and confocal microscopy, respectively. SMIT-1 was detected in endometrial tissue from all groups and decreased in PCOS and obesity ( P < 0.05 vs. normal weight ). In the in vitro model, PCOS conditions decreased p-AMPK levels, while they were restored with MYO ( P < 0.05). The diminished GLUT-4 protein levels promoted by PCOS environment were restored by MYO through SMIT-1 and p-AMPK-dependent mechanism ( P < 0.05). Also, MYO restored glucose uptake in cells under PCOS condition through a p-AMPK-dependent mechanism. Finally, these results were similar to those obtained with metformin treatment in the same in vitro conditions. Consequently, MYO could be a potential insulin sensitizer through its positive effects on insulin-resistant tissues as PCOS-endometrium, acting through SMIT-1, provoking AMPK activation and elevated GLUT-4 levels and, consequently, increase glucose uptake by human endometrial cells. Therefore, MYO may be used as an effective treatment option in insulin-resistant PCOS women.

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