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...
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| Vydané v: | PloS one Ročník 13; číslo 6; s. e0198323 |
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| Hlavní autori: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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United States
Public Library of Science
21.06.2018
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| ISSN: | 1932-6203, 1932-6203 |
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| Abstract | 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. |
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| AbstractList | 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. 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.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. |
| Audience | Academic |
| Author | Kovács, Dóra Lovászi, Marianna Szentkereszty-Kovács, Zita Hegyi, Katalin Póliska, Szilárd Zouboulis, Christos C. Szegedi, Andrea Ståhle, Mona Törőcsik, Dániel |
| AuthorAffiliation | San Gallicano Dermatologic Institute, ITALY 4 Division of Dermatological Allergology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary 3 Department of Biochemistry and Molecular Biology, Genomic Medicine and Bioinformatics Core Facility, Faculty of Medicine, University of Debrecen, Debrecen, Hungary 1 Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary 2 Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden 5 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodore Fontane, Dessau, Germany |
| AuthorAffiliation_xml | – name: 3 Department of Biochemistry and Molecular Biology, Genomic Medicine and Bioinformatics Core Facility, Faculty of Medicine, University of Debrecen, Debrecen, Hungary – name: 5 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodore Fontane, Dessau, Germany – name: San Gallicano Dermatologic Institute, ITALY – name: 2 Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden – name: 4 Division of Dermatological Allergology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary – name: 1 Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary |
| Author_xml | – sequence: 1 givenname: Dániel orcidid: 0000-0002-6094-6266 surname: Törőcsik fullname: Törőcsik, Dániel – sequence: 2 givenname: Dóra surname: Kovács fullname: Kovács, Dóra – sequence: 3 givenname: Szilárd surname: Póliska fullname: Póliska, Szilárd – sequence: 4 givenname: Zita surname: Szentkereszty-Kovács fullname: Szentkereszty-Kovács, Zita – sequence: 5 givenname: Marianna surname: Lovászi fullname: Lovászi, Marianna – sequence: 6 givenname: Katalin surname: Hegyi fullname: Hegyi, Katalin – sequence: 7 givenname: Andrea surname: Szegedi fullname: Szegedi, Andrea – sequence: 8 givenname: Christos C. surname: Zouboulis fullname: Zouboulis, Christos C. – sequence: 9 givenname: Mona surname: Ståhle fullname: Ståhle, Mona |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29927962$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:138640666$$DView record from Swedish Publication Index (Karolinska Institutet) |
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| Copyright | COPYRIGHT 2018 Public Library of Science 2018 Törőcsik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2018 Törőcsik et al 2018 Törőcsik et al |
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| SubjectTerms | Acne Acne Vulgaris - genetics Amyloid Analysis Biology and Life Sciences Cell Line Chemotaxis Clustering Cytokines Dermatology Diagnostic systems Endocrinology Epidermal growth factor Epithelial cells Gene expression Gene Expression Profiling - methods Gene Regulatory Networks - drug effects Genes Genomes Gram-negative bacteria Hazards High-Throughput Nucleotide Sequencing Humans Immune response Immune system Immunology Inflammation Inflammatory response Lipid metabolism Lipid Metabolism - drug effects Lipids Lipopeptides - pharmacology Lipopolysaccharides Lipopolysaccharides - pharmacology Medicine Medicine and Health Sciences Metabolism Pathogenesis Penicillin Phenotypes Propionibacterium acnes Proteins Receptors Rosacea Sebaceous gland Sebaceous glands Sebaceous Glands - cytology Sebaceous Glands - drug effects Sebaceous Glands - metabolism Sequence Analysis, RNA Serum Amyloid A Protein - genetics Skin Skin diseases TLR1 protein TLR4 protein Toll-Like Receptor 1 - metabolism Toll-Like Receptor 2 - metabolism Toll-Like Receptor 4 - metabolism Toll-like receptors Wound healing |
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| Title | 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 |
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