Interleukin-1 beta enhances and interferon-gamma suppresses activin A actions by reciprocally regulating activin A and follistatin secretion from bone marrow stromal fibroblasts.

Abstract:

:Activin A is a multi-functional cytokine with a potent stimulation on erythroid cell differentiation in the bone marrow. The actions of activin A are determined by a balance of the levels of activin A and its inhibitor, follistatin (FS). However, the regulation of its actions in the bone marrow has been unclear. Here we show that bone marrow-derived stromal fibroblasts are the major source of activin A and FS in the bone marrow, and that the production of activin A is enhanced by interleukin-1beta (IL-1beta) and lipopolysaccharide (LPS), whereas interferon-gamma (IFN-gamma) inhibits the secretion of activin A by stromal fibroblasts. Concomitantly, IL-1beta as well as LPS inhibits and IFN-gamma stimulates FS secretion from stromal fibroblasts. Thus, these cytokines potently regulate activin A actions by reciprocal modulation of activin A and FS secretion from stromal fibroblasts. Because activin A exhibits anti-inflammatory effects in various tissues, up-regulation of activin A actions by IL-1beta and endotoxin in the bone marrow may play a protective role against inflammatory processes as well as anaemia. The present results also suggest that the inhibitory effect of IFN-gamma on erythropoiesis is mediated at least in part by a suppression of activin A actions in bone marrow.

journal_name

Clin Exp Immunol

authors

Abe M,Shintani Y,Eto Y,Harada K,Fujinaka Y,Kosaka M,Matsumoto T

doi

10.1046/j.1365-2249.2001.01644.x

subject

Has Abstract

pub_date

2001-10-01 00:00:00

pages

64-8

issue

1

eissn

0009-9104

issn

1365-2249

pii

1644

journal_volume

126

pub_type

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