Acute regulation of activin A and its binding protein, follistatin, in serum and tissues following lipopolysaccharide treatment of adult male mice

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

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21 Citations (Scopus)

Abstract

Activin A, a member of the transforming growth factor-beta family, increases in the circulation within one hour after administration of bacterial lipopolysaccharide (LPS). In order to clarify the origins of this rapid increase, the distribution of activin A and its binding protein, follistatin, and their production following LPS-treatment, were assessed in adult male mice. In untreated mice, activin A was detectable in all 23 tissues examined, with highest mRNA expression (measured by quantitative RT-PCR) in the liver, and the largest concentration of activin A protein (by ELISA) in the bone marrow. Likewise, follistatin mRNA and protein were present in all tissues, with highest expression in the vas deferens. Activin A and follistatin mRNA did not increase significantly in any tissue within the first hour after LPS, but activin A protein decreased by 35 in the bone marrow and increased 5-fold in the lung. No significant changes were observed in any other tissue. Activin A reached a peak in the circulation one hour following LPS, then declined. Cycloheximide, an inhibitor of protein translation, reduced this increase of activin A by more than 50 . Actinomycin D, an inhibitor of mRNA transcription, had no effect. Circulating follistatin did not increase until 4 hours after LPS, and was not affected by either inhibitor. These data indicate that the rapid increase in circulating activin A during LPS-induced inflammation is regulated at the post-transcriptional level, apparently from newly-translated and stored protein, and implicate bone marrow-derived cells, and neutrophils in particular, as a significant source of this pre-formed activin A.
Original languageEnglish
Pages (from-to)R-665 - R-675
Number of pages11
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume303
Issue number6
DOIs
Publication statusPublished - 2012

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