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* Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and
Department of Research, Introgen Therapeutics Inc., Houston, TX 77030; and
Corixa Corp., Seattle, WA 98104
The melanoma differentiation-associated gene 7
(mda-7) has been studied primarily in the context
of its tumor suppressor activity. Although mda-7 has
been designated as IL-24 based on its gene location in the
IL-10 locus and its mRNA expression in leukocytes, no
functional evidence supporting this cytokine designation exists. To
further characterize MDA-7/IL-24 expression patterns in the human
immune system, MDA-7/IL-24 protein levels were examined in human PBMC.
MDA-7/IL-24 was detected in PHA- and LPS-stimulated whole PBMC lysate
by Western blot and in PHA-activated CD56 and CD19 subsets by
immunohistochemistry. The biological function of MDA-7/IL-24, secreted
from Ad-MDA7-transfected HEK 293 cells, was assessed by examining the
effect of MDA-7/IL-24 on the cytokine secretion profile of PBMC. Within
48 h MDA-7/IL-24 induced secretion of high levels of IL-6,
TNF-
, and IFN-
and low levels of IL-1
, IL-12, and GM-CSF from
human PBMC as measured by ELISA. The MDA-7/IL-24-mediated induction of
these Th1-type cytokines was inhibited by the addition of IL-10 to the
PBMC cultures, suggesting that these two related protein family members
may provide antagonistic functions. Therefore, because human blood
leukocytes can be stimulated to produce MDA-7/IL-24, as well as respond
to MDA-7/IL-24 by expressing secondary cytokines, MDA-7/IL-24 has the
expression profile and major functional attributes that justify its
designation as an IL.
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