Expression of interleukin-13 receptor alpha 1-subunit on peripheral blood eosinophils is regulated by cytokines.
Interleukin-13 (IL-13) is critical for the development of allergic asthma and is involved in the activation of eosinophils within the airways. IL-13 exerts its activity on target cells via the dimeric IL-13 receptor (IL-13R), which comprises the IL-13 receptor alpha1-chain (IL-13Ralpha1) as a specific component. The aim of this study was to investigate the expression of the IL-13Ralpha1-chain on primary human eosinophilic granulocytes. Furthermore, it addresses the regulatory influence of cytokines on the level of surface abundance of this receptor subunit. Expression of IL-13- and IL-4-receptor subunits in purified primary human eosinophils was monitored at the messenger RNA level by reverse transcription polymerase chain reaction and at the protein level by flow cytometry. For the analysis of IL-13Ralpha1 surface expression, a new monoclonal antibody, which was generated using genetic immunization, was employed. Different cytokines with established activity on eosinophils were studied with regard to their influence on IL-13Ralpha1 in vitro by flow cytometry. Whereas IL-13 and IL-4 had inhibitory effects on IL-13Ralpha1 expression on eosinophils, interferon-gamma, tumour necrosis factor-alpha, and, to the largest extent, transforming growth factor-beta, enhanced the expression of this receptor subunit. A positive regulatory response evoked by transforming growth factor-beta and interferon-gamma does not prevent inhibitory effects caused by IL-13. These findings suggest a regulatory cytokine network influencing the reactivity of eosinophils to IL-13.
Department of Pneumology, University Hospital Freiburg, Freiburg, Germany.
Daniel
D
Myrtek
Mathias
M
Knoll
Timm
T
Matthiesen
Sebastian
S
Krause
Jens
J
Lohrmann
Dirk
D
Schillinger
Marco
M
Idzko
J Christian
JC
Virchow
Karlheinz
K
Friedrich
Werner
W
Luttmann
D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology; D053661:Interleukin-13 Receptor alpha1 Subunit; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000097:blood* / Q000235:genetics; D053660:Receptors, Interleukin-13; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D016207:Cytokines; C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D016212:Transforming Growth Factor beta