IL-4 down-regulates IL-2 receptor p75 by accelerating its endocytosis.
We examined the effects of interleukin 4 (IL-4) on the expression of IL-2 receptor p75 (IL-2R p75) or beta chain on various human T cells. IL-4 promptly down-regulated surface IL-2 receptor (IL-2R) p75 in these cells. Although IL-2-induced IL-2R p75 down-regulation was seen more quickly, IL-2 did not contribute to the process of the IL-4-induced decrease of IL-2R p75. Northern blotting revealed that IL-4 did not reduce the expression of IL-2R p75 mRNA. Studies using Pronase E, which digests cell surface IL-2R p75, or brefeldin A, which blocks intracytoplasmic protein transport from endoplasmic reticulum to the Golgi apparatus, suggest that IL-4-induced IL-2R p75 down-regulation is controlled after IL-2R p75 is expressed on the cell surface. We found that IL-4 accelerated the endocytosis of IL-2R p75, which was monitored by [125I]Mik-beta 3 monoclonal antibody that recognizes non-IL-2-binding epitope on IL-2R p75. These findings demonstrate that IL-4 down-regulates IL-2R p75 mainly by accelerating its endocytosis.
Ishikawa
T
T
First Division of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Uchiyama
T
T
Kamio
M
M
Onishi
R
R
Kodaka
T
T
Okuma
M
M
D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D015536:Down-Regulation; D004705:Endocytosis; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D015375:Receptors, Interleukin-2; D015847:Interleukin-4