A single intracerebral microinjection of platelet-derived growth factor (PDGF) accelerates the rate of remyelination in vivo.

We had demonstrated that platelet-derived growth factor (PDGF) enhanced the reconstruction of myelin-like membranes after their disruption by lysophosphatidylcholine (LPC) in vitro. To investigate its role in vivo, a demyelinating lesion of the corpus callosum was induced in adult Wistar rats by a stereotaxic microinjection of 1 microl LPC, then 63 pairs of rats received either 1 microg PDGF, or its vehicle buffer which were injected above LPC. The effects of PDGF were significant after 2 weeks: the number of oligodendrocytes (OL) expressing 2',3'-cyclic nucleotide 3'-phosphodiesterase in the lesion increased by 49%, mature OL labelled by in situ hybridization for myelin basic protein-mRNA increased by 27% (P<10(-2)), and the total volume of demyelination decreased by 60% compared to controls.

Hepatocyte-derived cell lines express a functional receptor for cardiotrophin-1.

Cardiotrophin-1 (CT-1) is a recently isolated cytokine belonging to the interleukin-6 cytokine family. In the present study, we show that CT-1 binds to hepatocyte-derived cell lines of rat and human origin with high (Kd = 600-800 pM) and low (Kd approximately 3-6 nM) binding affinities. Treatment of HepG2 cells with CT-1 resulted in the induction of tyrosine phosphorylation of both transducing receptor subunits, gp130 and LIF receptor, and this phosphorylation was completely inhibited by a neutralizing anti-gp130 mAb.

Signaling of type II oncostatin M receptor.

Oncostatin M (OSM) mediates its bioactivities through two different heterodimer receptors. They both involve the gp130-transducing receptor, which dimerizes with either leukemia inhibitory receptor beta or with OSM receptor beta (OSMRbeta) to generate, respectively, type I and type II OSM receptors. Co-precipitation of gp130-associated proteins, flow cytometry, polymerase chain reaction, and tyrosine phosphorylation analyses allowed the characterization of both types of OSM receptors expressed on the surface of different cell lines.

Signaling of the cardiotrophin-1 receptor. Evidence for a third receptor component.

Cardiotrophin-1 (CT-1) is a recently isolated cytokine belonging to the interleukin-6 cytokine family. In the present study we show that CT-1 activates its receptor expressed at the surface of a human neural cell line by recruiting gp130 and gp190/leukemia inhibitory factor receptor beta, as shown by analyzing their tyrosine phosphorylation level. Neutralizing antibody directed against gp130 and reconstitution experiments performed in the COS-7 cell line demonstrate that gp130-gp190 heterocomplex formation is essential for CT-1 signaling.

Alanine substitution for Thr268 and Asp269 of soluble ciliary neurotrophic factor (CNTF) receptor alpha component defines a specific antagonist for the CNTF response.

Ciliary neurotrophic factor (CNTF) associates with an alpha subunit (CNTFRalpha) of the receptor complex to initiate signal transduction by facilitating heterodimerization of the gp130 transducing protein and the leukemia inhibitory factor receptor (LIFR) beta. CNTFRalpha is anchored to the membrane by a glycosylphosphatidylinositol linkage; however, a soluble form of the alpha subunit can still bind CNTF to recruit the signal transducing components of the receptor complex. In the present study we show that alanine substitution for residues Thr268 and Asp269 of the CNTFRalpha subunit results in a mutated receptor subunit (R3), which can bind CNTF with an affinity similar to that of the wild type CNTFRalpha but, when expressed as a soluble receptor subunit, lowers the binding of CNTF to its tripartite receptor.