Novel Neurotrophin-1/B Cell-Stimulating Factor-3: A Cytokine of the IL-6 Family

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 20; pp. 11458 - 11463
• Main Authors: Senaldi, G, Varnum, B C, Sarmiento, U, Starnes, C, Lile, J, Scully, S, Guo, J, Elliott, G, McNinch, J, Shaklee, C L, Freeman, D, Manu, F, Simonet, W S, Boone, T, Chang, M S
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 28.09.1999; National Acad Sciences; The National Academy of Sciences
• Subjects: AB cell-stimulating factor 3; Amino Acid Sequence; Animals; Apolipoproteins - biosynthesis; B cell-stimulating factor 3; B lymphocytes; Base Sequence; Biological Sciences; Body Weight - drug effects; Cell Division - drug effects; Chick Embryo; chromosome 11; Complementary DNA; Corticosterone; Corticosterone - biosynthesis; Cytokines; Female; glycoprotein gp130; Humans; Immunoglobulin G - blood; Immunoglobulin M - blood; Interleukin-1 - pharmacology; Interleukin-6 - genetics; Interleukin-6 - isolation & purification; Interleukin-6 - pharmacology; leukemia inhibitory factor receptor b; Liver; Lymph nodes; Lymphoid Tissue - drug effects; Messenger RNA; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Neurons; neurotrophin 1; neurotrophins; RNA; RNA, Messenger - analysis; serum amyloid A; Serum Amyloid A Protein - biosynthesis; tyrosine phosphorylation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.20.11458

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.