Complex of the soluble IL-11 receptor and IL-11 acts as IL-6-type cytokine in hepatic and nonhepatic cells.
The signaling functions of the membrane and soluble form of the mouse IL-11 receptor (mIL-11R) were compared in rat and human hepatoma cells, which have a low endogenous IL-11 response. The expression vectors encoding either the full length or a secretory form of the ligand binding subunit of mIL-11R together with IL-6-responsive reporter gene constructs were transiently transfected into the H-35 and HepG2 cells. An IL-11-specific stimulation of transcription was detected that was qualitatively similar to that mediated by the endogenous IL-6R. HepG2 cells were noted to synthesize constitutively IL-11, resulting in an autocrine stimulation of gene expression. Addition of COS cell-derived soluble mIL-11R to the hepatoma cell cultures prominently enhanced IL-11 regulation of transfected reporter gene constructs and expression of endogenous acute phase plasma protein genes. Similarly, the complex of soluble mIL-11R and IL-11 was capable of mediating an IL-6-type signaling in cells that are naturally deficient in IL-11 response as shown by the activation of STAT1 and STAT3 in mouse embryonal carcinoma cells and human T cells. The results indicate that the IL-11R can serve as a substitute to IL-6R in activating gene expression in target cells that are devoid of the appropriate ligand-binding receptor subunits.
Baumann
H
H
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Wang
Y
Y
Morella
K K
KK
Lai
C F
CF
Dams
H
H
Hilton
D J
DJ
Hawley
R G
RG
Mackiewicz
A
A
D000818:Animals; D001483:Base Sequence; D018236:Carcinoma, Embryonal / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D006801:Humans; D017370:Interleukin-11 / Q000502:physiology*; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6 / Q000031:analogs & derivatives* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000276:immunology*; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D018123:Receptors, Interleukin / Q000502:physiology*; D053702:Receptors, Interleukin-11; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
C508428:IL11RA protein, human; C508429:Il11ra1 protein, mouse; C508430:Il11ra1 protein, rat; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6; D046911:Macromolecular Substances; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11