Role of TGF-β1 on the IgE-Dependent Anaphylaxis Reaction

Abstract

TGF-β1 is a member of a family of polypeptide factors that control proliferation, differentiation, chemotaxis, and other functions in many cell types. TGF-β1 has been shown to inhibit many immunologic functions. However, here we report that TGF-β1 has an important role in the elicitation of IgE-dependent allergic reactions. The synthetic antisense TGF-β1 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-β1 oligonucleotides was added, significantly increased ∼7-fold compared with that of basal cells. The antisense TGF-β1 oligonucleotides also had a significant inhibitory effect on anti-DNP IgE-induced TNF-α release from mast cells. In situ hybridization analysis showed that the PCA reaction sites treated with antisense TGF-β1 oligonucleotides exhibited no detectable levels of TGF-β1 and l-histidine decarboxylase mRNA after anti-DNP IgE stimulation, whereas the PCA reaction sites treated with sense TGF-β1 oligonucleotides possessed significant amounts of their mRNA. Additionally, neutralizing Ab to TGF-β1 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-β1 is critical to the development of IgE-dependent anaphylaxis reactions.