Abstract
Nicotinic acid (NA) activates hydroxycarboxylic acid receptor 2 (HCA2), and it is widely used in treating dyslipidaemias. Since its side effects include skin dryness, whereas its deficiency can be accompanied by dyssebacia, characterized by sebaceous gland enlargement, we asked if HCA2 is expressed on human sebocytes, and if NA influences sebocyte functions. By using human immortalized SZ95 sebocytes, we found that non‐cytotoxic (≤100 μmol/L; MTT‐assay) concentrations of NA had no effect on the homeostatic sebaceous lipogenesis (SLG; Nile Red), but normalized excessive, acne‐mimicking SLG induced by several lipogenic agents (arachidonic acid, anandamide, linoleic acid + testosterone; Nile Red; 48‐hr treatments). Moreover, it exerted significant anti‐proliferative actions (CyQUANT‐assay), and increased [Ca2+]IC (Fluo‐4 AM‐based Ca2+‐measurement). Although NA did not prevent the lipopolysaccharide‐induced pro‐inflammatory response (up‐regulation [Q‐PCR] and release [ELISA] of several pro‐inflammatory cytokines) of the sebocytes, collectively, these data support the concept that NA may be effective in suppressing sebum production in vivo. While exploring the mechanism of the sebostatic actions, we found that sebocytes express HCA2 (Q‐PCR, immunofluorescent labelling), siRNA‐mediated silencing of which prevented the NA‐induced Ca2+‐signal and the lipostatic action. Collectively, our data introduce NA, and HCA2 activators in general, as novel, potent and most likely safe sebostatic agents, with possible anti‐acne potential.
Highlights
Acne is one of the most common human skin diseases
Since its side effects include skin dryness, whereas its deficiency can be accompanied by dyssebacia, characterized by sebaceous gland enlargement, we asked if hydroxycarboxylic acid receptor 2 (HCA2) is expressed on human sebocytes, and if Nicotinic acid (NA) influ‐ ences sebocyte functions
By using human immortalized SZ95 sebocytes, we found that non‐cytotoxic (≤100 μmol/L; MTT‐assay) concentrations of NA had no effect on the homeostatic sebaceous lipogenesis (SLG; Nile Red), but normalized excessive, acne‐mimicking SLG induced by several lipogenic agents
Summary
Acne is one of the most common human skin diseases. It impairs quality of life of millions of patients world‐wide, and is characterized by excessively increased and qualitatively altered sebaceous lipo‐ genesis (SLG), complex inflammatory processes, as well as abnormal skin—microbiota cross‐talk.[1,2,3,4] highly efficient anti‐acne agents (eg isotretinoin) exist, their administration is often limited by different (sometimes quite serious) side effects.[1,2] there is an unmet need from both the scientific community and society to develop novel, highly efficient therapeutic agents exhibiting better side effect and safety profiles. When applied at pharmacological doses, side ef‐ fects of NA include skin dryness (https://www.drugs.com/pro/ niacin.html), whereas NA deficiency can be accompanied by seba‐ ceous gland enlargement.[6] pilot clinical studies demon‐ strate that high doses of orally administered NA may exert beneficial effects against acne.[18,19,20] based on the aforementioned data, we hypothesized that NA may directly impact on the biology of human sebocytes, and that these actions might be mediated via HCA2 receptors. Considering the regret‐ table limitations of the available model systems to study sebaceous gland biology, including ineffective culturing of primary human se‐ bocytes and the lack of adequate animal model systems,[3,21,22] we decided to use the human immortalized SZ95 sebocyte cell line,[22,23] a widely accepted and reliable model to study human sebaceous gland biology in vitro.[2,3,22,23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
