M. Lovászi

Sebocytes differentially express and secrete adipokines.

In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte‐associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression profile of adipokines [adiponectin, interleukin (IL) 6, resistin, leptin, serpin E1, visfatin, apelin, chemerin, retinol‐binding protein 4 (RBP4) and monocyte chemoattractant protein 1 (MCP1)] in sebaceous glands of healthy and various disease‐affected (acne, rosacea, melanoma and psoriasis) skin samples. Sebaceous glands in all examined samples expressed adiponectin, IL6, resistin, leptin, serpin E1 and visfatin, but not apelin, chemerin, RBP4 and MCP1. Confirming the presence of the detected adipokines in the human SZ95 sebaceous gland cell line we further characterized their expression and secretion patterns under different stimuli mimicking bacterial invasion [by using Toll‐like receptor (TLR)2 and 4 activators], or by 13‐cis retinoic acid (13CRA; also known as isotretinoin), a key anti‐acne agent. With the exception of resistin, the expression of all of the detected adipokines (adiponectin, IL6, leptin, serpin E1 and visfatin) could be further regulated at the level of gene expression, showing a close correlation with the secreted protein levels. Besides providing further evidence on similarities between adipocytes and sebocytes, our results strongly suggest that sebocytes are not simply targets of inflammation but may exhibit initiatory and modulatory roles in the inflammatory processes of the skin through the expression and secretion of adipokines.

Leptin promotes a proinflammatory lipid profile and induces inflammatory pathways in human SZ95 sebocytes

Leptin, the adipocyte‐secreted hormone that regulates weight, is known to link lipid metabolism with inflammation in various cell types. However, its role in human sebocytes has not yet been investigated.

Sebum lipids influence macrophage polarization and activation

As lipids are known to regulate macrophage functions, it is reasonable to suppose that a sebocyte–macrophage axis mediated by sebum lipids may exist.

Sebocytes contribute to skin inflammation by promoting the differentiation of Th17 cells

The main function of sebocytes is considered to be the production of lipids to moisturize the skin. However, it recently became apparent that sebocytes release chemokines and cytokines and respond to proinflammatory stimuli as well as the presence of bacteria.

Genome wide analysis of TLR1/2- and TLR4-activated SZ95 sebocytes reveals a complex immune-competence and identifies serum amyloid A as a marker for activated sebaceous glands

Toll-like receptors (TLR) 2 and 4 are active in sebaceous glands and play a central role in the development of acne. Still, there is only limited knowledge on their effect on sebocytes. In this work we performed global gene expression profile analysis with functional clustering of the differentially regulated genes of TLR1/2 (PAM3CSK4)- and TLR4 (lipopolysaccharide [LPS])-activated SZ95 sebocytes. Both TLR1/2- and 4-activation promoted inflammation in a similar manner already at an early time-point (6 hours), regulating genes involved in inflammation, wound healing and chemotaxis reflecting a more complex cytokine and chemokine regulation than previously known. Importantly, lipid metabolism, the primary feature of sebocytes, was affected at the level of gene expression only at a later time point (24 hours) indicating that sebocytes prioritize to exert a pro-inflammatory phenotype when confronted with a danger signal. Supporting the biological relevance of our results, a meta-analysis revealed that the genes showing the strongest up-regulation were also found up-regulated in acne. Of these genes, serum amyloid A 1/2 (SAA1/2) was confirmed to be a suitable protein marker for in vivo activated sebocytes, underlining their immune-competence, which is structurally defined within sebaceous glands of acne and rosacea skin samples. Altogether our findings demonstrate that sebocytes are not only positioned at the end point of inflammation but are actively involved in shaping the inflammatory response with putative diagnostic and therapeutic relevance.

Sebaceous-immunobiology is orchestrated by sebum lipids

ABSTRACT The major role of sebaceous glands in mammals is to produce sebum, which coats the epidermis and the hair providing waterproofing, thermoregulation and photoprotection. However, as the need for these functions decreased along the evolutionary changes in humans, a relevant question has been raised: are sebaceous glands and sebum the remnants of our mammalian heritage or do they have overtaken a far more complex role in human skin biology? Trying to provide answers to this question, this review introduces the evolving field of sebaceous immunobiology and puts into the focus the pathways that sebum lipids use to influence the immune milieu of the skin. By introducing possible modifiers of sebaceous lipogenesis and discussing the – human-specific – alterations in composition and amount of sebum, the attribute of sebum as a sensitive tool, which is capable of translating multiple signalling pathways into the dermal micro environment is presented. Further their interaction with macrophages and keratinocytes involves sebum lipid fractions into disease pathogenesis, which could lead – on the other side – to the development of novel sebum-based therapeutic strategies.