| Interleukin-18 system plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions. | |
| | |
MedLine Citation:
|
PMID: 22050194 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Background: Keloid scarring is a dermal fibroproliferative disorder characterized by increased fibroblast proliferation and excessive production of collagen-extracellular matrix (ECM) components. To date, the role of cytokines in the keloid pathogenesis has not been completely unraveled. Interleukin-18 (IL-18) is a pro-inflammatory cytokine that plays important roles in wound healing, fibrogenesis and carcinogenesis, and our aim was to study the role of IL-18 sytem in keloid pathogenesis. Methods and Findings: Results from Western blot and immunohistochemistry revealed that IL-18, IL-18Rα and IL-18Rβ expression were elevated in keloid tissue compared with normal skin tissue. Studies on the expression of IL-18 and its antagonist, IL-18 binding protein (IL-18BP) using a coculture model demonstrated severe IL-18/IL-18BP imbalance in keloid keratinocyte/keloid fibroblast cocultures with significant elevation of bioactive IL-18 whereas IL-18BP levels remained the same. This overproduction of bioactive IL-18 in keloid cocultures could be due to increased Caspase-1 and decreased Caspase-3 expression in keloid tissue, as well as decreased soluble IL-10 levels observed in keloid cocultures. The important inductive effects of IL-18 on keloid fibroblasts (KF) were further underscored by the observation that exposure of KF to IL-18 resulted in increased collagen-ECM component synthesis, and increased secretion of profibrotic cytokines such as IL-6 and IL-8. Finally, addition of PI3K, MAPK, Sp1 and mTOR inhibitors inhibited IL-18 secretion in keloid cocultures. Conclusions: The present study has proven that the IL-18 system plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions. It also suggests a therapeutic potential of PI3K, MAPK, Sp1 and mTOR inhibitors in the treatment of keloid scarring. |
| | |
Authors:
|
D V Do; C T Ong; Y T Khoo; A Carbone; C P Lim; S Wang; A Mukhopadhyay; X Cao; D H Cho; X Q Wei; G Bellone; I Lim; T T Phan |
Related Documents
:
|
10786654 - Uses of granulocyte-macrophage colony-stimulating factor in vaccine development. 20350814 - Il-17 is elevated in cerebrospinal fluids in bacterial meningitis in children. 10556204 - Granulocyte-macrophage colony-stimulating factor induces expression of heparin-binding ... 12060844 - G-csf: function and modes of action (review). 21904534 - Modulation of mucosal immune response, tolerance, and proliferation in mice colonized b... 19352074 - Inhibition of phenotypic and functional maturation of dendritic cells by manassantin a. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-11-4 |
Journal Detail:
|
Title: The British journal of dermatology Volume: - ISSN: 1365-2133 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
|
Created Date: 2011-11-4 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0004041 Medline TA: Br J Dermatol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 British Association of Dermatologists. |
Affiliation:
|
Department of Surgery Faculty of Dentistry-Centre for Craniofacial and Regenerative Biology Department of Microbiology Department of Pharmacy NUS Tissue Engineering and Stem Cell Research Program, National University of Singapore, Singapore Institute of Molecular and Cell Biology, Proteos, Singapore Department of Clinical Physiopathology, University of Turin, Turin, Italy Department of Gastroenterology and Clinical Nutrition, Azienda Ospedaliera San Giovanni Battista, Molinette, Turin, Italy Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea Department of Dental Health and Biological Sciences, Cardiff University, Cardiff, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A Carbohydrate-Conjugated Deep Cavitand Permits Observation of Caviplexes in Human Serum.
Next Document: Hydroxychloroquine retinopathy combined with retinal pigment epithelium detachment.