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

Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11458-63. doi: 10.1073/pnas.96.20.11458.

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 beta, 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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apolipoproteins / biosynthesis
  • Base Sequence
  • Body Weight / drug effects
  • Cell Division / drug effects
  • Chick Embryo
  • Corticosterone / biosynthesis
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Interleukin-1 / pharmacology
  • Interleukin-6 / genetics
  • Interleukin-6 / isolation & purification*
  • Interleukin-6 / pharmacology
  • Lymphoid Tissue / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • RNA, Messenger / analysis
  • Serum Amyloid A Protein / biosynthesis

Substances

  • Apolipoproteins
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Serum Amyloid A Protein
  • Corticosterone

Associated data

  • GENBANK/AF176911
  • GENBANK/AF176912
  • GENBANK/AF176913