Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130.
The interleukin-6 (IL-6) signal is transduced through membrane-anchored gp130, which is associated with IL-6 receptor (IL-6R) in the presence of IL-6. Soluble forms of gp130 (sgp130) with molecular weights of 90 and 110 Kd were found in human serum. In the presence of recombinant IL-6 (rIL-6), serum sgp130 were capable of associating with serum sIL-6R. By the sandwich enzyme-linked immunosorbent assay, healthy human sera was shown to contain 390 +/- 72 ng/mL of sgp130. A mouse pro-B-cell line-derived transfectant, BAF-130, expressing human gp130 was used to examine the function of serum sgp130. When supplemented with rIL-6, human serum induced DNA synthesis in BAF-130 cells, whereas the serum deprived of sIL-6R did not. In contrast, the DNA synthesis induced in BAF-130 cells by rIL-6-supplemented serum was increased when the serum was deprived of sgp130. These results indicated that serum sgp130 could negatively regulate the IL-6 signal. Recently, gp130 has been shown to be involved in the signaling processes of oncostatin M, leukemia inhibitory factor, and ciliary neurotropic factor, in addition to those of IL-6. Recombinant sgp130 showed inhibitory effect on the biologic function of such cytokines. This work implies physiologic roles of naturally produced serum sgp130 in modulating signals through gp130.
Narazaki
M
M
Division of Immunology, Osaka University, Japan.
Yasukawa
K
K
Saito
T
T
Ohsugi
Y
Y
Fukui
H
H
Koishihara
Y
Y
Yancopoulos
G D
GD
Taga
T
T
Kishimoto
T
T
D000818:Animals; D015703:Antigens, CD; D050822:Cytokine Receptor gp130; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000097:blood / Q000502:physiology*; D051379:Mice; D011817:Rabbits; D011971:Receptors, Immunologic / Q000032:analysis / Q000502:physiology*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction
D015703:Antigens, CD; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130