Tumor necrosis factor alpha enhances the expression of the interleukin (IL)-4 receptor alpha-chain on endothelial cells increasing IL-4 or IL-13-induced Stat6 activation.
Functional receptors for interleukin (IL)-4 and IL-13 on endothelial cells consist of the 130-kDa IL-4 receptor alpha-chain (IL-4Ralpha) and a 65-75-kDa IL-13 binding subunit that are expressed in a ratio of about 1:3, respectively. The restricted number of IL-4Ralpha limits subunit heterodimerization and in turn receptor-mediated signaling. We report here, the effects of tumor necrosis factor alpha (TNF-alpha) on the expression of the receptor subunits for IL-4 and IL-13. By flow cytofluorometry and receptor-binding analysis of iodinated IL-4 and IL-13, stimulation with TNF-alpha-induced a 2-3-fold increase of the IL-4Ralpha expression. The up-regulation was also confirmed at the transcriptional level by reverse transcription-polymerase chain reaction. Radioligand cross-linking experiments revealed no change in the subunit composition of the TNF-alpha-induced receptor complex. Nevertheless, TNF-alpha stimulation led to increased activation of the IL-4-specific signal transducers and activators of transcription protein (Stat6) by IL-4 and IL-13. Thus, TNF-alpha corrects the subunit imbalance of the endothelial IL-4.IL-13 receptor complex thereby increasing receptor heterodimerization and in turn the signaling capability by IL-4 and IL-13.
Lugli
S M
SM
Institute of Toxicology, Federal Institute of Technology, CH-8057 Zurich, Switzerland.
Feng
N
N
Heim
M H
MH
Adam
M
M
Schnyder
B
B
Etter
H
H
Yamage
M
M
Eugster
H P
HP
Lutz
R A
RA
Zurawski
G
G
Moser
R
R
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008958:Models, Molecular; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D015534:Trans-Activators / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
D015703:Antigens, CD; D018793:Interleukin-13; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases