A complex of the soluble interleukin-6 receptor and interleukin-6 is internalized via the signal transducer gp130.
In human body fluids a soluble form of the interleukin-6 receptor (sIL-6R) has been found which together with interleukin-6 (IL-6) acts agonistically on cells expressing the signal transducer gp130. The means by which the sIL-6R is removed from the circulation is unknown. Here, we show that a complex of 125I-labelled recombinant sIL-6R and IL-6 is internalized by MDCK cells stably transfected with gp130 and by human hepatoma cells HepG2 that endogenously express the IL-6R and gp130. We further show that most of the internalized sIL-6R is degraded within lysosomes. Our studies suggest that cells expressing gp130 are capable of endocytosing an IL-6/sIL-6R complex, thereby removing both from the circulation.
Graeve
L
L
Institut für Biochemie, Rheinisch-Westfälische Technische Hochschule Aachen, Germany.
Korolenko
T A
TA
Hemmann
U
U
Weiergräber
O
O
Dittrich
E
E
Heinrich
P C
PC
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D050822:Cytokine Receptor gp130; D004285:Dogs; D004705:Endocytosis; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130