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Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Chonbuk, South Korea
TGF-ß1 is a member of a family of polypeptide factors that
control proliferation, differentiation, chemotaxis, and other functions
in many cell types. TGF-ß1 has been shown to inhibit many immunologic
functions. However, here we report that TGF-ß1 has an important role
in the elicitation of IgE-dependent allergic reactions. The synthetic
antisense TGF-ß1 oligonucleotides dose-dependently inhibit passive
cutaneous anaphylaxis (PCA) reaction and histamine release from the
mast cells activated by anti-DNP IgE in rats. The level of cAMP in
mast cells, when antisense TGF-ß1 oligonucleotides was added,
significantly increased
7-fold compared with that of basal cells.
The antisense TGF-ß1 oligonucleotides also had a significant
inhibitory effect on anti-DNP IgE-induced TNF-
release from mast
cells. In situ hybridization analysis showed that the PCA reaction
sites treated with antisense TGF-ß1 oligonucleotides exhibited no
detectable levels of TGF-ß1 and L-histidine decarboxylase
mRNA after anti-DNP IgE stimulation, whereas the PCA reaction sites
treated with sense TGF-ß1 oligonucleotides possessed significant
amounts of their mRNA. Additionally, neutralizing Ab to TGF-ß1
blocked the PCA reaction significantly, but its Ab did not inhibit
peritoneal mast cell-released histamine upon treatment with
anti-DNP IgE. Our results suggest that TGF-ß1 is critical to the
development of IgE-dependent anaphylaxis
reactions.
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