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Innate Immune Dysfunction in Rosacea Promotes Photosensitivity and Vascular Adhesion Molecule Expression.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2020 Mar; Vol. 140 (3), pp. 645-655.e6. Date of Electronic Publication: 2019 Aug 29. - Publication Year :
- 2020
-
Abstract
- Rosacea is a chronic skin disease characterized by photosensitivity, abnormal dermal vascular behavior, inflammation, and enhanced expression of the antimicrobial peptide LL-37. We observed that dermal endothelial cells in rosacea had an increased expression of VCAM1 and hypothesized that LL-37 could be responsible for this response. The digestion of double-stranded RNA from keratinocytes exposed to UVB blocked the capacity of these cells to induce adhesion molecules on dermal microvascular endothelial cells. However, a synthetic noncoding snoU1RNA was only capable of increasing adhesion molecules on endothelial cells in the presence of LL-37, suggesting that the capacity of UVB exposure to promote both double-stranded RNA and LL-37 was responsible for the endothelial response to keratinocytes. Sequencing of RNA from the endothelial cells uncovered the activation of Gene Ontology (GO) pathways relevant to the human disease, such as type I and II interferon signaling, cell-cell adhesion, leukocyte chemotaxis, and angiogenesis. Functional relevance was demonstrated as double-stranded RNA and LL-37 promoted adhesion and transmigration of monocytes across the endothelial cell monolayers. Gene knockdown of TLR3, RIGI, or IRF1 decreased monocyte adhesion in endothelial cells, confirming the role of the double-stranded RNA recognition pathways. These observations show how the expression of LL-37 can lead to enhanced sensitivity to UVB radiation in rosacea.<br /> (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antimicrobial Cationic Peptides genetics
Biopsy
Cell Adhesion immunology
Cell Line
Cell Movement immunology
Disease Models, Animal
Endothelial Cells metabolism
Endothelium, Vascular cytology
Endothelium, Vascular metabolism
Female
Gene Expression Regulation immunology
Humans
Immunity, Innate genetics
Keratinocytes
Mice
Mice, Transgenic
Microvessels cytology
Microvessels metabolism
Photosensitivity Disorders pathology
RNA, Double-Stranded metabolism
RNA, Small Nuclear metabolism
Rosacea immunology
Rosacea pathology
Signal Transduction genetics
Signal Transduction immunology
Skin blood supply
Skin immunology
Skin pathology
Skin radiation effects
THP-1 Cells
Ultraviolet Rays adverse effects
Cathelicidins
Antimicrobial Cationic Peptides metabolism
Immunity, Innate immunology
Photosensitivity Disorders immunology
Rosacea complications
Vascular Cell Adhesion Molecule-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 140
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 31472105
- Full Text :
- https://doi.org/10.1016/j.jid.2019.08.436