Tropoelastin regulates chemokine expression in fibroblasts in Costello syndrome
- Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505 (Japan)
- Glyco-Chain Expression Laboratory, Supra-Biomolecular System Research Group, RIKEN Frontier Research System, Saitama 351-0198 (Japan)
- Department of Pediatrics, Akita University of Medical School, Akita 010-8543 (Japan)
- Department of Analytical Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588 (Japan)
Costello syndrome is a multiple congenital anomaly associated with growth and mental retardation, cardiac and skeletal anomalies, and a predisposition to develop neoplasia. Comprehensive expression analysis revealed remarkable up-regulation of several cytokines and chemokines including Gro family proteins, interleukin-1{beta} (IL-1{beta}), IL-8 and MCP-1 but down-regulation of extracellular matrix components including collagens and proteoglycans of skin fibroblasts derived from a Japanese Costello syndrome patient characterized by significantly reduced tropoelastin mRNA, impaired elastogenesis and enhanced cell proliferation. In contrast, decreases in these chemokines and IL-1{beta} expression were observed in Costello fibroblastic cell lines stably expressing the bovine tropoelastin (btEln) gene and in restored elastic fibers. These results strongly suggest that the human TE gene (ELN) transfer could be applicable for the gene therapy of a group of Costello syndrome patients with reduced ELN gene expression.
- OSTI ID:
- 21143799
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 372, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2008.05.131; PII: S0006-291X(08)01017-6; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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