Expression and secretion of interleukin-1ß, tumour necrosis factor-α and interleukin-10 by hypoxia- and serum-deprivation-stimulated mesenchymal stem cells.
FEBS J
; 277(18): 3688-98, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20681988
ABSTRACT
To understand the potential paracrine roles of interleukin-1ß (IL-1ß), 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-1ß and TNF-α transcription. Furthermore, hypoxia/SD stimulated the translation of pro-IL-1ß and its processing to mature IL-1ß, although the translation of TNF-α was unchanged. Unexpectedly, the release of IL-1ß and TNF-α from hypoxia/SD-stimulated mesenchymal cells was undetectable unless ATP or lipopolysaccharide was present. This result suggests that IL-1ß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
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Regulação da Expressão Gênica
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Fator de Necrose Tumoral alfa
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Interleucina-10
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Comunicação Parácrina
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Interleucina-1beta
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Células-Tronco Mesenquimais
Limite:
Animals
Idioma:
En
Revista:
FEBS J
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
China