Novel neurotrophin-1/B cell-stimulating factor-3: A cytokine of the IL-6 family

Giorgio Senaldi, Brian C. Varnum, Charlie Starnes Ulla Sarmiento, Jackson Lile, Sheila Scully, Jane Guo, Gary Elliott, Jennifer McNinch, Christine L. Shaklee, Daniel Freeman, Frank Manu, W. Scott Simonet, Thomas Boone, Ming Shi Chang

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Abstract

We have identified a cytokine of the IL-6 family and named it novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3). NNT-1/BSF-3 cDNA was cloned from activated Jurkat human T cell lymphoma cells. Its sequence predicts a 225-aa protein with a 27-aa signal peptide, a molecular mass of 22 kDa in mature form, and the highest homology to cardiotrophin-1 and ciliary neurotrophic factor. The gene for NNT-1/BSF-3 is on chromosome 11q13. A murine equivalent to NNT-1/BSF-3 also was identified, which shows 96% homology to human NNT-1/BSF-3. NNT-1/BSF-3 mRNA is found mainly in lymph nodes and spleen. NNT-1/BSF-3 induces tyrosine phosphorylation of glycoprotein 130 (gp130), leukemia inhibitory factor receptor β, and signal transducer and activator of transcription 3 in the SK-N-MC human neuroblastoma cells. NNT-1/BSF-3 shows activities typical of IL-6 family members. In vitro, it supports the survival of chicken embryo motor and sympathetic neurons. In mice, it induces serum amyloid A, potentiates the induction by IL-1 of corticosterone and IL-6, and causes body weight loss and B cell hyperplasia with serum IgG and IgM increase. NNT-1/BSF-3 is a gp130 activator with B-cell stimulating capability.

Original languageEnglish
Pages (from-to)11458-11463
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number20
DOIs
Publication statusPublished - 1999 Sep 28

All Science Journal Classification (ASJC) codes

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    Senaldi, G., Varnum, B. C., Ulla Sarmiento, C. S., Lile, J., Scully, S., Guo, J., Elliott, G., McNinch, J., Shaklee, C. L., Freeman, D., Manu, F., Scott Simonet, W., Boone, T., & Chang, M. S. (1999). Novel neurotrophin-1/B cell-stimulating factor-3: A cytokine of the IL-6 family. Proceedings of the National Academy of Sciences of the United States of America, 96(20), 11458-11463. https://doi.org/10.1073/pnas.96.20.11458