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TRPV3 mediates Propionibacterium acnes-induced chemotaxis and inflammation in sebocytes

ABSTRACT: TRPV3 is highly expressed in human skin and is involved in the development of inflammatory dermatoses. However, it remains unclear whether TRPV3 influences inflammation in human sebaceous glands and its role in the pathogenesis of acne. Here, we showed that TRPV3 expression was increased in the sebaceous glands of facial acne lesions and acne-like mice. TRPV3 increased the secretion of pro-inflammatory cytokines and chemokines in human SZ95 sebocytes, as well as the chemotaxis of neutrophils, which were the major immune cells found in acne lesions. We demonstrated that P.acnes promoted TRPV3 expression through regulating lipid profile especially upregulated arachidonic acid levels in human sebocytes. TRPV3 further upregulated TLR2 expression by promoting transcriptional factor p-FOSL1 expression and its binding to the TLR2 promoter, leading to downstream NF-κB signaling activation. Importantly, either genetic silencing or pharmacological inhibition of TRPV3 alleviated acne-like inflammation in mice, showing reduced acne-characteristic cytokines and chemokines production and neutrophil infiltration by inhibiting the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebocytes inflammation, which was involved in the development of acne, indicating that TRPV3 is a potential therapeutic target for acne and other disorders of the pilosebaceous unit.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245001 | GEO | 2023/10/13

REPOSITORIES: GEO

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Project description:This SuperSeries is composed of the following subset Series:; GSE10432: 13-cis retinoic acid treatment of human sebocytes (SEB-1); GSE10433: Human Skin: Before and 1 week after Isotretinoin Treatment; The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of cultured human immortalized sebocytes (SEB-1) treated with 13-cis RA was performed to gain insights into its sebocyte-specific mechanism of action. SEB-1 sebocytes were cultured with 0.1 uM 13-cis RA for 72 hours or vehicle control. Gene array expression profiling was conducted using Affymetrix HG-U95Av2 arrays in order to examine changes in gene expression as a result of treatment. A total of 85 genes (78 different genes) were significantly influenced by 13-cis RA: 58 were upregulated and 27 were down-regulated. There were changes in several genes involved in apoptosis and innate immunity. These studies are the first describing the sebocyte- specific response in gene expression associated with isotretinoin therapy and are valuable in identifying potential therapeutic targets in acne. The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of skin from 6 patients treated with isotretinoin was performed to gain insights into its mechanism of action. Skin biopsies were obtained from the patients at baseline and at one-week isotretinoin treatment. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays in order to examine changes in gene expression as a result of treatment. After treatment, 43 genes were significantly changed: 38 up-regulated and 5 down-regulated. A significant proportion of these genes are involved in pathways that regulate differentiation, tumor suppression, serine proteases, serine protease inhibitors and solute transfer. These studies are the first describing the initial changes in gene expression associated with isotretinoin therapy and are valuable in identifying potential therapeutic targets in acne. Experiment Overall Design: Refer to individual Series

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TRPV3 mediates Propionibacterium acnes-induced chemotaxis and inflammation in sebocytes

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