Rm. Nusing et J. Barsig, Induction of prostanoid, nitric oxide, and cytokine formation in rat bone marrow derived macrophages by activin A, BR J PHARM, 127(4), 1999, pp. 919-926
1 In this study we describe that activin A, a transforming growth factor (T
GF) beta-like polypeptide affects the expression of inflammatory response g
enes and their products.
2 In rat bone marrow derived macrophages 15 nM activin A caused the stimula
tion of prostaglandin (PG) E-2 and thromboxane (TX) A(2) formation, product
ion of nitrite as a marker for nitric oxide (NO) and the release of the cyt
okines tumour necrosis factor (TNF) alpha and interleukin (IL) -1 beta. As
shown by mRNA analysis induction of cyclo-oxygenase-2 and inducible nitric
oxide synthase by activin A gave rise to the enhanced release of prostanoid
s and NO.
3 Costimulation of bone marrow derived macrophages with 15 nM activin A and
100 nM 12-O-tetradecanoyl-phorbol 13-acetate (TPA) potentiated the synthes
is of prostanoids in a synergistic manner. With respect to NO formation the
effect of activin A and TPA was additive.
4 In contrast to the nitrite production activin A induced PGE(2) synthesis
was susceptible to tyrosine kinase inhibition by genistein and tyrphostin 4
6 (IC50 was 10 and 20 mu M, respectively). This observed inhibition was cau
sed by the selective suppression of activin A induced cyclo-oxygenase-2 mRN
A expression. Further, the release of TNF alpha in the presence of activin
A was potentiated by tyrosine kinase inhibition.
5 In summary, we report that activin A exerts proinflammatory activity whic
h results in the formation of prostanoids, NO and cytokines in rat bone mar
row derived macrophages. Tyrosine kinase dependent and independent signalli
ng pathways are involved leading to the increased synthesis of these metabo
lites. Based upon these results, we speculate that activin A may be conside
red as a possible component of inflammatory processes affecting at least th
e haematopoietic system.