Functional Implications of the Il-6 Signaling Pathway in Keloid Pathogenesis.
From: Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan. ciem@nms.ac.jp
The Journal of investigative dermatology
- Publish Date: Jan 2007
- ISSN: 1523-1747
- Volume: 127
- Issue: 1
- Pages: 98-105
- Medium: Internet
- Language: English
- Citation (JAMA): Ghazizadeh Mohammad, Tosa Mamiko, Shimizu Hajime, et al. Functional Implications of the Il-6 Signaling Pathway in Keloid Pathogenesis.. J. Invest. Dermatol. Jan 2007;127:98-105
Abstract
The molecular mechanism(s) behind keloid pathogenesis remains unclear. Previously by global gene expression analysis of keloid fibroblasts (KFs), we implicated the IL-6 signaling pathway in keloid pathogenesis. Here, we determine a functional role of IL-6 signaling in keloid scars. Primary cultures of KFs and surrounding nonlesional fibroblasts (NFs) were subjected to induction or inhibition of IL-6 or its specific receptor IL-6 receptor alpha (IL-6R alpha) and detection of their effects on extracellular matrix gene expression. The levels of gp130 and several downstream targets in IL-6 signaling were also examined. IL-6 secretion was significantly higher in KFs than NFs. Addition of IL-6 peptide to NFs culture or inhibition of IL-6 or its receptor IL-6R alpha by their corresponding antibodies in KFs culture revealed a dose-dependent increase or decrease in collagen type I alpha 2 and fibronectin 1 mRNAs, respectively. Induction of IL-6 by IL-1beta peptide and stimulation by IL-6 peptide in NFs, or inhibition of IL-6 or IL-6R alpha in KFs cultures demonstrated a dose-dependent increase or decrease in procollagen I synthesis, respectively. The mRNA and protein expressions of gp130 and several downstream targets in IL-6 signaling (JAK1, STAT3, RAF1, and ELK1) were upregulated in KFs versus NFs. Our results indicate that IL-6 signaling may play an integral role in keloid pathogenesis and provide clues for development of IL-6 receptor blocking strategies for therapy or prophylaxis of keloid scars.
Mesh Headings (Keywords): Adult, Cell Proliferation, Cells, Cultured, Collagen, Female, Fibroblasts, Humans, Interleukin-6, Keloid, Proto-Oncogene Proteins c-raf, RNA, Messenger, Receptors, Interleukin-6, STAT3 Transcription Factor, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 17024100
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.