Disease relevance of CNTF

• Analysis of the specificity of action of GPA showed that, in addition to E8 ciliary ganglion neurons, the factor was able to support short-term survival of E8 dorsal root ganglion and E12 sympathetic neurons [1].
• We can prevent apoptosis, due either to NGF or CNTF withdrawal and in either type of neuron, by overexpression of a mutant inactive ICE and an ICE inhibitor, the product of cowpox virus gene crmA [2].
• C6 mRNA was size-fractionated, and fractions encoding CNTF-like activity were cloned into a lambda phage vector at a site distal to a T7 promoter [3].
• Rat C6 glioma cells, which had been previously shown to have CNTF-like activity (Westermann et al., 1988), were used as source material [3].
• Different aspects of gliosis in retinal Muller glia can be induced by CNTF, insulin, and FGF2 in the absence of damage [4].

High impact information on CNTF

• We have previously reported the purification of a ciliary neurotrophic factor from adult chick sciatic nerve that we called growth promoting activity (GPA) [5].
• Amino acid sequence of a proteolytic digestion fragment of GPA revealed homology with the recently published sequences for rabbit and rat sciatic nerve CNTF [1].
• The biological activity of GPA differed from that of FGF in that it was not potentiated by heparin and did not stimulate mitogenesis in chick fibroblasts [1].
• In addition, CNTF affects the differentiation of sympathetic ganglion cells by inducing the expression of vasoactive intestinal peptide immunoreactivity (VIP-IR) [6].
• Bcl-2 does not prevent apoptosis in CNTF-dependent ciliary neurons or DRG neurons as it does in NGF-dependent neurons [2].

Chemical compound and disease context of CNTF

• CNTF also induced the tyrosine phosphorylation of a similar protein in cultured chick dorsal root ganglion and retinal neurons [7].
• Ciliary ganglion neurons extend neuritic processes when cultured for 24 h in medium containing ciliary neuronotrophic factor (CNTF) and on a polyornithine substratum precoated with either laminin or a Schwannoma-derived neurite promoting factor (PNPF) [8].
• Treatment of cultured cardiomyocytes and retinal and ciliary ganglion neurons with retinoic acid resulted in increased expression of receptors for the neuropoietic cytokine, CNTF [9].

Biological context of CNTF

• Ciliary neutrophic factor (CNTF) can enhance motoneuron survival during naturally occurring cell death in the chick (Oppenheim et al, 1991) [10].
• Complete depletion of NGF or CNTF from culture medium induces apoptosis in both types of neurons [2].
• Immunoprecipitation experiments with rat footpad extracts provided evidence for the presence of ChAT-inducing factors other than CNTF, which may independently or together with CNTF be involved in the determination of sympathetic neuron phenotype [11].
• The down-regulation of alpha-bungarotoxin binding sites on neurons caused by CNTF occurs with a half-time of about 19 hr and is largely reversed within a 4 d period following CNTF removal [12].
• We show here that a factor indistinguishable from CNTF specifically down-regulates alpha-bungarotoxin binding sites on the neurons while increasing cell growth and the number of ACh receptors on the cells [12].

Anatomical context of CNTF

• Conditioned medium produced by cultured retinal cells (most likely glial cells) exhibited opsin stimulating activity identical to that of CNTF [13].
• CNTF has no effect on the number of ACh receptors found on chick myotubes in culture [12].
• Immunohistochemical analysis of P21 rat footpads demonstrated CNTF-like immunoreactivity in Schwann cells but not in sweat glands, the target tissue of cholinergic sympathetic neurons [11].
• Our results suggest that CNTF acted as an inductive signal for uncommitted progenitor cells or during early stages of rod photoreceptor differentiation, whereas other extrinsic stimulatory activities seemed to be required for further maturation [13].
• Either NGF or CNTF also elicited neurite outgrowth from rat chromaffin cells, which amounted to approximately 15-20% at D1 and D8 and subsequently decreased to about 5-8% at D30 and virtually zero at D100 [14].

Associations of CNTF with chemical compounds

• When addition was delayed for 3 d, CNTF failed to elicit increases either in the number of cholinergic neurons or in GABA uptake [15].
• Here we show that CNTF induced the rapid tyrosine phosphorylation and nuclear accumulation of this protein and identify it as an avian form of the transcription factor, STAT3 [7].
• The distribution of chick CNTF was altered neither by brefeldin A nor by chloroquine treatment [16].
• The active species in RCM has a molecular weight (20,900 +/- 1,000) identical to that of CNTF, as determined by preparative sodium dodecyl sulfate gel electrophoresis [17].
• These results indicate that neurons and myocytes expressing CNTF receptors are responsive to retinoic acid and suggest that retinoids may regulate cell sensitivity to cytokines during development [9].

Regulatory relationships of CNTF

• CNTFRalpha-mediated signal transduction was demonstrated in E7 and E11 DRG neuron cultures by CNTF-induced STAT3 phosphorylation [18].
• RT-PCR and Northern blot analysis, however, showed that rhodopsin mRNA was undetectable in both control and CNTF-treated cultures but that CNTF induced significant increases in mRNA levels for the green cone pigment [19].

Other interactions of CNTF

• In addition, we identify a second, 100-kDa form of STAT3 that appears in response to CNTF [7].
• The number of cells acquiring opsin immunoreactivity, determined after 3 days in vitro, was increased up to 4-fold in the presence of CNTF to maximally 10.5% of all cells [13].
• The EC50 of the CNTF effect (2.6 pM) was virtually identical to that measured for other CNTF receptor mediated cellular responses [13].
• We show here that a CNTF-like, VIP-inducing activity is present in rat footpads and that its increases 6-fold during the period of cholinergic sympathetic differentiation [11].
• Ciliary neurotrophic factor (CNTF) is a neuropoietic cytokine that was identified, purified, and cloned based on its neurotrophic activity on cultured chick ciliary ganglion neurons [7].

Analytical, diagnostic and therapeutic context of CNTF

• Ciliary neuronotrophic factor (CNTF) has been shown to enhance the survival of ciliary ganglion neurons in cell culture and has been postulated to act as a target-derived trophic factor for the neurons in vivo [12].
• Ciliary neurotrophic factor (CNTF) has been purified 35,000-fold to homogeneity from rabbit sciatic nerves using its ability to promote the survival of chick embryo ciliary ganglion neurons as the bioassay [20].
• Although the punctate pattern of chick CNTF immunoreactivity was not due to reuptake, chick CNTF could be found in a cellular compartment labeled after a brief incubation with dextran microbeads [16].
• When this ciliary neuronotrophic factor (CNTF) was concentrated using ultrafiltration and subjected to Sephadex G100 and G200 chromatography, activity was detected in most of the eluted fractions [21].
• These results show that although CNTF has no effect on naturally occurring death of chick or mouse sensory neurons, this agent has significant ability to rescue sensory neurons following axotomy [22].

References