Effects of Eupatilin on Insulin-Like Growth Factor 1-Induced Lipogenesis and Inflammation of SZ95 Sebocytes.
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ABSTRACT:
SUBMITTER: Lee JH
PROVIDER: S-EPMC7992769 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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Effects of Eupatilin on Insulin-Like Growth Factor 1-Induced Lipogenesis and Inflammation of SZ95 Sebocytes.
Lee Ji Hyun JH Lee Ye Jin YJ Song Ji Young JY Kim Yeong Ho YH Lee Jun Young JY Zouboulis Christos C CC Park Young Min YM
Annals of dermatology 20190701 4
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Project description:Epidermal growth factor (EGF) acts as a paracrine and autocrine mediator of cell proliferation and differentiation in various types of epithelial cells, such as sebocytes, which produce the lipid-rich sebum to moisturize the skin. However, sebum lipids via direct contact and by penetrating through the epidermis may have regulatory roles on epidermal and dermal cells as well. As EGF receptor (EGFR) is expressed throughout the proliferating and the lipid-producing layers of sebaceous glands (SGs) in healthy and acne-involved skin, we investigated the effect of EGF on SZ95 sebocytes and how it may alter the changes induced by palmitic acid (PA), a major sebum component with bioactive roles. We found that EGF is not only a potent stimulator of sebocyte proliferation, but also induces the secretion of interleukin (IL)6 and down-regulates the expression of genes involved in steroid and retinoid metabolism. Importantly, when applied in combination with PA, the PA-induced lipid accumulation was decreased and the cells secreted increased IL6 levels. Functional clustering of the differentially regulated genes in SZ95 sebocytes treated with EGF, PA or co-treated with EGF+PA further confirmed that EGF may be a potent inducer of hyperproliferative/inflammatory pathways (IL1 signaling), an effect being more pronounced in the presence of PA. However, while a group of inflammatory genes was up-regulated significantly in EGF+PA co-treated sebocytes, PA treatment in the absence of EGF, regulated genes only related to cell homeostasis. Meta-analysis of the gene expression profiles of whole acne tissue samples and EGF- and EGF+PA -treated SZ95 sebocytes showed that the EGF+PA co-activation of sebocytes may also have implications in disease. Altogether, our results reveal that PA-induced lipid accumulation and inflammation can be modulated by EGF in sebocytes, which also highlights the need for system biological approaches to better understand sebaceous (immuno)biology.
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Project description:Insulin-like growth factor-1 (IGF-1) is considered as a pathogenic factor contributing to sebaceous gland dysfunction, which leads to acne vulgaris. Paeoniflorin (Pae), a bioactive monomer derived from total glycosides of paeony, has shown potential in treating various diseases. However, its anti-acne effects on human sebocytes are not well understood. In this study, we investigated the effects of Pae on acne development induced by IGF-1 in SZ95 sebocytes. Following IGF-1 stimulation, SZ95 sebocytes were exposed to Pae and then determined for proliferation, cell cycle, apoptosis, lipogenesis and pro-inflammatory cytokine secretion. We also analyzed the expression of proteins involved in the PI3K/Akt/FoxO1 and JAK2/STAT3 pathways. In vitro experiments demonstrated that Pae significantly inhibited colony formation, induced G1/S cell cycle arrest, promoted apoptosis, inhibited lipogenesis and cytokine synthesis in IGF-1-treated SZ95 sebocytes. Furthermore, Pae suppressed the phosphorylation of Akt, FoxO1, JAK2, and STAT3. Importantly, the sebo-suppressive and anti-inflammatory effects of Pae were enhanced by blocking PI3K and JAK2. In summary, our findings suggest that Pae has potent anti-proliferative and pro-apoptotic effects in SZ95 sebocytes. Additionally, Pae effectively protects against IGF-1-induced lipogenesis and inflammation by targeting the PI3K/Akt/FoxO1 and JAK2/STAT3 signaling pathways.
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Project description:BackgroundAfzelin, a flavonoid (kaempferol 3-O-α-L-rhamnopyranoside) isolated from Thesium chinense, is known for its potent anti-inflammatory properties. However, its effects on the molecular aspects of inflammation and lipogenesis in SZ95 sebocytes has not been investigated.ObjectiveThis study aimed to (i) investigate inflammatory and sebum secretion changes when a Cutibacterium acnes-treated immortalized human sebocyte cell line (SZ95) is exposed to particulate matter (PM) and (ii) examine the effects of afzelin on these.MethodsTo investigate the effect of afzelin on PM- and C. acnes-treated SZ95 sebocytes, we injected heat-killed C. acnes into SZ95 cells to induce acne-like status. Thereafter, the SZ95 sebocytes were treated with PM and subsequently with afzelin. The gene expression profile was determined using real-time polymerase chain reaction analysis, and protein expression was confirmed via western blotting and immunofluorescence. Intracellular lipid droplet formation was investigated using Nile Red O staining.ResultsPM treatment upregulated the mRNA and protein expression levels of inflammatory cytokine and lipogenic genes in C. acnes-treated SZ95 sebocytes. Furthermore, intracellular lipid-droplet accumulation increased when C. acnes-stimulated SZ95 cells were exposed to PM. Interestingly, the upregulated inflammatory and lipogenic gene expression induced by C. acnes and PM was attenuated by afzelin treatment.ConclusionsThis study's findings indicate that PM potentially aggravates acne by acting on both inflammation and sebum secretion. They also reveal afzelin's ability to suppress these phenomena by not only suppressing inflammatory cytokine expression but also inhibiting sebogenesis. These findings confirm afzelin's potential therapeutic role in improving PM-exacerbated acne.
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Project description:Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free fatty acids (FFAs) to produce the lipid-rich sebum. Importantly, like other sebum components such as palmitic acid (PA), LA and its derivative arachidonic acid (AA) are known to modulate sebocyte functions. Given the different roles of PA, LA and AA in skin biology, the aim of this study was to assess the specificity of sebocytes for LA and to dissect the different roles of LA and AA in regulating sebocyte functions. Using RNA sequencing, we confirmed that gene expression changes in LA-treated sebocytes were largely distinct from those induced by PA. LA, but not AA, regulated the expression of genes related to cholesterol biosynthesis, androgen and nuclear receptor signalling, keratinisation, lipid homeostasis and differentiation. In contrast, a set of mostly down-regulated genes involved in lipid metabolism and immune functions overlapped in LA- and AA-treated sebocytes. Lipidomic analyses revealed that the changes in the lipid profile of LA-treated sebocytes were more pronounced than those of AA-treated sebocytes, suggesting that LA may serve not only as a precursor of AA but also as a potent regulator of sebaceous lipogenesis, which may not only influence the gene expression profile but also have further specific biological relevance. In conclusion, we have shown that sebocytes are able to respond selectively to different lipid stimuli and that LA-induced effects can be both AA-dependent and independent. Our findings allow for the consideration of LA application in the therapy of sebaceous gland-associated inflammatory skin diseases such as acne, where lipid modulation and selective targeting of AA metabolism are potential treatment options.
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