Expression and secretion of interleukin-1β, tumour necrosis factor-α and interleukin-10 by hypoxia- and serum-deprivation-stimulated mesenchymal stem cells
| Autor: | Zongwei, Li, Hua, Wei, Linzi, Deng, Xiangfeng, Cong, Xi, Chen |
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| Rok vydání: | 2010 |
| Předmět: |
Time Factors
Tumor Necrosis Factor-alpha Myocardium Interleukin-1beta Transcription Factor RelA Bone Marrow Cells Heart Mesenchymal Stem Cells Fibrosis Interleukin-10 Rats Rats Sprague-Dawley Animals Newborn Gene Expression Regulation Stress Physiological Paracrine Communication Animals RNA Messenger Protein Precursors Cells Cultured |
| Zdroj: | The FEBS journal. 277(18) |
| ISSN: | 1742-4658 |
| Popis: | To understand the potential paracrine roles of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10), the expression and secretion of these factors by rat bone marrow-derived mesenchymal cells stimulated by hypoxia (4% oxygen) and serum deprivation (hypoxia/SD) were investigated. We found that hypoxia/SD induced nuclear factor kappa Bp65-dependent IL-1β and TNF-α transcription. Furthermore, hypoxia/SD stimulated the translation of pro-IL-1β and its processing to mature IL-1β, although the translation of TNF-α was unchanged. Unexpectedly, the release of IL-1β and TNF-α from hypoxia/SD-stimulated mesenchymal cells was undetectable unless ATP or lipopolysaccharide was present. This result suggests that IL-1β and TNF-α are not responsible for the paracrine effects of mesenchymal cells under ischaemic conditions. We also found that hypoxia/SD induced the transcription and secretion of IL-10, which were significantly enhanced by lipopolysaccharide and the proteasomal inhibitor MG132. Moreover, both the conditioned medium from hypoxia/SD-stimulated mesenchymal cells (MSC-CM) and IL-10 efficiently inhibited cardiac fibroblast proliferation and collagen expression in vitro, suggesting that mesenchymal cell-secreted IL-10 prevents cardiac fibrosis in a paracrine manner under ischaemic conditions. Taken together, these findings may improve understanding of the cellular and molecular basis of the anti-inflammatory and paracrine effects of mesenchymal cells. |
| Databáze: | OpenAIRE |
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