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Autocrine activation by interleukin 1alpha induces the fibrogenic phenotype of systemic sclerosis fibroblasts.
- Source :
-
The Journal of rheumatology [J Rheumatol] 2004 Oct; Vol. 31 (10), pp. 1946-54. - Publication Year :
- 2004
-
Abstract
- Objective: To explore the cellular localization of interleukin 1alpha (IL-1alpha) in cultured fibroblasts from lesional skin of patients with systemic sclerosis (SSc) and to study the role of intracellular IL-1alpha in the activation of fibroblasts.<br />Methods: Dermal fibroblasts were derived from 12 patients with SSc. Expression of IL-1alpha mRNA was examined using reverse transcriptase-polymerase chain reaction (RT-PCR). The cellular distribution of IL-1alpha was examined by subcellular fractionation, flow cytometry, and immunocytochemistry. A full-length IL-1alpha cDNA was subcloned into the pcDNA3 vector to create sense and antisense-encoding constructs. Normal and SSc fibroblasts were stably transfected with the sense and antisense-encoding constructs, respectively. Stably transfected fibroblast clones were analyzed for the production of procollagen and IL-6 protein by ELISA, alpha1(I) procollagen mRNA by Northern blot hybridization, and proliferation by [3H]thymidine incorporation.<br />Results: SSc-affected fibroblasts constitutively expressed intracellular IL-1alpha, which was predominantly located in the nucleus. Inhibition of IL-1alpha expression in SSc-affected fibroblasts using antisense constructs resulted in decreased proliferation, IL-6 production, and procollagen synthesis. Conversely, overexpression of IL-1alpha in normal fibroblasts resulted in development of the SSc fibroblast phenotype.<br />Conclusion: IL-1alpha is an important autocrine fibrogenic factor in SSc, suggesting that inhibition of intracellular IL-1alpha may be a novel strategy for the treatment of SSc.
- Subjects :
- Cell Proliferation
Cells, Cultured
Fibroblasts cytology
Fibrosis
Humans
Interleukin-1 genetics
Interleukin-6 metabolism
Oligonucleotides, Antisense genetics
Oligonucleotides, Antisense metabolism
Phenotype
Procollagen metabolism
RNA, Messenger metabolism
Subcellular Fractions metabolism
Autocrine Communication
Fibroblasts physiology
Interleukin-1 metabolism
Scleroderma, Systemic immunology
Scleroderma, Systemic pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0315-162X
- Volume :
- 31
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of rheumatology
- Publication Type :
- Academic Journal
- Accession number :
- 15468358