Abstract | BACKGROUND:
Keloid scarring is a dermal fibroproliferative disorder characterized by increased fibroblast proliferation and excessive production of collagen and extracellular matrix (ECM) components. To date, the role of cytokines in keloid pathogenesis has not been completely unravelled. Interleukin (IL)-18 is a pro-inflammatory cytokine that plays important roles in wound healing, fibrogenesis and carcinogenesis. OBJECTIVES: Our aim was to study the role of the IL-18 system in keloid pathogenesis. MATERIALS AND METHODS: Expression and localization of IL-18 and its receptor (IL-18R) were investigated in normal skin and keloid tissues using Western blot and immunohistochemistry. We further studied the expression of the IL-18 system in normal and keloid-derived cell lines in a coculture model. RESULTS: 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.
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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 |
Journal | The British journal of dermatology
(Br J Dermatol)
Vol. 166
Issue 6
Pg. 1275-88
(Jun 2012)
ISSN: 1365-2133 [Electronic] England |
PMID | 22050194
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2012 The Authors. BJD © 2012 British Association of Dermatologists 2012. |
Chemical References |
- Enzyme Inhibitors
- Interleukin-18
- Interleukin-6
- Interleukin-8
- Receptors, Interleukin-18
- Sp1 Transcription Factor
- Collagen
- MTOR protein, human
- TOR Serine-Threonine Kinases
- Mitogen-Activated Protein Kinase Kinases
- Caspase 3
- Caspase 1
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Topics |
- Caspase 1
(metabolism)
- Caspase 3
(metabolism)
- Cells, Cultured
- Collagen
(metabolism)
- Enzyme Inhibitors
(pharmacology)
- Epithelial-Mesenchymal Transition
(physiology)
- Fibroblasts
(drug effects, metabolism)
- Humans
- Interleukin-18
(pharmacology, physiology)
- Interleukin-6
(metabolism)
- Interleukin-8
(metabolism)
- Keloid
(etiology)
- Keratinocytes
(drug effects, metabolism)
- Mitogen-Activated Protein Kinase Kinases
(metabolism)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Receptors, Interleukin-18
(metabolism)
- Sp1 Transcription Factor
(metabolism)
- TOR Serine-Threonine Kinases
(metabolism)
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