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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.
PLoS One. 2018; 13(6):e0198323.Plos

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.

Authors+Show Affiliations

Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.Department of Biochemistry and Molecular Biology, Genomic Medicine and Bioinformatics Core Facility, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Division of Dermatological Allergology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodore Fontane, Dessau, Germany.Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29927962

Citation

Törőcsik, Dániel, et al. "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." PloS One, vol. 13, no. 6, 2018, pp. e0198323.
Törőcsik D, Kovács D, Póliska S, et al. 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. PLoS ONE. 2018;13(6):e0198323.
Törőcsik, D., Kovács, D., Póliska, S., Szentkereszty-Kovács, Z., Lovászi, M., Hegyi, K., Szegedi, A., Zouboulis, C. C., & Ståhle, M. (2018). 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. PloS One, 13(6), e0198323. https://doi.org/10.1371/journal.pone.0198323
Törőcsik D, et al. 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. PLoS ONE. 2018;13(6):e0198323. PubMed PMID: 29927962.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Törőcsik,Dániel, AU - Kovács,Dóra, AU - Póliska,Szilárd, AU - Szentkereszty-Kovács,Zita, AU - Lovászi,Marianna, AU - Hegyi,Katalin, AU - Szegedi,Andrea, AU - Zouboulis,Christos C, AU - Ståhle,Mona, Y1 - 2018/06/21/ PY - 2017/12/14/received PY - 2018/05/17/accepted PY - 2018/6/22/entrez PY - 2018/6/22/pubmed PY - 2018/12/12/medline SP - e0198323 EP - e0198323 JF - PloS one JO - PLoS ONE VL - 13 IS - 6 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/29927962/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_ L2 - http://dx.plos.org/10.1371/journal.pone.0198323 DB - PRIME DP - Unbound Medicine ER -