Role of TGF-beta 1 on the IgE-dependent anaphylaxis reaction.
TGF-beta1 is a member of a family of polypeptide factors that control proliferation, differentiation, chemotaxis, and other functions in many cell types. TGF-beta1 has been shown to inhibit many immunologic functions. However, here we report that TGF-beta1 has an important role in the elicitation of IgE-dependent allergic reactions. The synthetic antisense TGF-beta1 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-beta1 oligonucleotides was added, significantly increased approximately 7-fold compared with that of basal cells. The antisense TGF-beta1 oligonucleotides also had a significant inhibitory effect on anti-DNP IgE-induced TNF-alpha release from mast cells. In situ hybridization analysis showed that the PCA reaction sites treated with antisense TGF-beta1 oligonucleotides exhibited no detectable levels of TGF-beta1 and L-histidine decarboxylase mRNA after anti-DNP IgE stimulation, whereas the PCA reaction sites treated with sense TGF-beta1 oligonucleotides possessed significant amounts of their mRNA. Additionally, neutralizing Ab to TGF-beta1 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-beta1 is critical to the development of IgE-dependent anaphylaxis reactions.
Kim
H M
HM
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Chonbuk, South Korea. hmkim@med.wonk.wang.ac.kr
Lee
Y M
YM
D000818:Animals; D006636:Histamine Release / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors / Q000235:genetics; D007106:Immune Sera / Q000494:pharmacology; D007073:Immunoglobulin E / Q000502:physiology*; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D007106:Immune Sera; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E; D006640:Histidine Decarboxylase