Regulation of activin A release from murine bone marrow-derived neutrophil precursors by tumour necrosis factor-alpha and insulin

Hui Wu, Yi Chen, Wendy Rachael Winnall, David James Phillips, Mark Peter Hedger

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15 Citations (Scopus)

Abstract

Activin A, a transforming growth factor-beta family cytokine, plays a crucial role in regulating the onset and severity of many inflammatory conditions, such as acute lipopolysaccharide (LPS)-induced inflammation. Activin A is also implicated in type 2 diabetes (T2D), a disease characterised by insulin resistance, hyperglycaemia and chronic elevation of pro-inflammatory cytokines, including tumour necrosis factor (TNF-alpha). In the human, neutrophils contain activin A that can be released in response to TNF-alpha. Studies of inflammatory disease in vivo, however, generally use the mouse, so it is essential to know if murine neutrophils have similar properties. Regulation of activin A was investigated in bone marrow-derived neutrophil precursors (BMNPs) from 8 to 10weeks old C57BL6/J male mice. The BMNPs contained 7-fold higher concentrations of activin A than bone marrow mononuclear cells. Release of activin A from isolated BMNPs was stimulated by TNF-alpha, but this was not due to increased activin A production. In contrast to TNF-alpha, LPS had no effect on isolated BMNPs, but stimulated activin A release and production in total bone marrow cell cultures. Moreover, activin A release in response to LPS, was not prevented in TNF-alpha null mice. Increased glucose and insulin had no effect on base-line activin A secretion by BMNPs in culture, but pre-treatment with insulin blocked the TNF-alpha induced release of activin A. These results indicate that murine neutrophils are a source of stored activin A, the release of which can be directly stimulated by TNF-alpha, although TNF-alpha is not the only stimulator of activin A release during inflammation. Furthermore, regulation of neutrophil activin A release by insulin may also play a role in the inflammation associated with T2D.
Original languageEnglish
Pages (from-to)199 - 204
Number of pages6
JournalCytokine
Volume61
Issue number1
DOIs
Publication statusPublished - 2013

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