D. Steinhilber et al., TRANSFORMING GROWTH-FACTOR-BETA UP-REGULATES 5-LIPOXYGENASE ACTIVITY DURING MYELOID CELL MATURATION, Proceedings of the National Academy of Sciences of the United Statesof America, 90(13), 1993, pp. 5984-5988
Transforming growth factor beta (TGFbeta) increased the arachidonate 5
-lipoxygenase (5-LO; EC 1.13. 11.34) activity in HL-60 cells induced t
o granulocytic differentiation by dimethyl sulfoxide. The presence of
a factor in human serum that caused a similar increase was recently de
monstrated. Several observations indicate that the serum factor consis
ts of isoforms of TGFbeta. Heat-treated serum and TGFbeta both resulte
d in almost-equal-to 10-fold increased 5-LO activity of HL-60 cells, a
ntiserum to TGFbeta neutralized the 5-LO-increasing activity in serum,
and physical properties of the serum factor (lipophilic nature, alkal
ine pI, stability to heat and acid) coincided with those of TGFbeta. T
he pattern of activity of native and heat-treated sera is compatible w
ith activation of a latent form of TGFbeta in serum. This activity was
specific for TGFbeta, since none of several other cytokines could inc
rease 5-LO activity in differentiating HL-60 cells. However, granulocy
te/macrophage-colony-stimulating factor (GM-CSF) and tumor necrosis fa
ctor a enhanced the effect of TGFbeta. The most prominent effects of T
GFbeta, whether alone or together with GM-CSF, were observed for 5-LO
activity in intact cells (10-fold or 30-fold induction, respectively).
5-LO protein levels were less affected (up to 2- or 5-fold, respectiv
ely, as judged from Western blots). There was no appreciable effect of
TGFbeta, or a combination of TGFbeta and GM-CSF, on 5-LO mRNA express
ion.