Cloning of human thymic stromal lymphopoietin (TSLP) and signaling mechanisms leading to proliferation

Leukemia. 2001 Aug;15(8):1286-92. doi: 10.1038/sj.leu.2402175.

Abstract

Thymic stromal lymphopoietin (TSLP) is a novel cytokine that was found to promote the development of murine B cells in vitro. Here we describe the cloning and characterization of the human homologue of murine TSLP. This protein, which is expressed in a number of tissues including heart, liver and prostate, prevented apoptosis and stimulated growth of the human acute myeloid leukemia (AML)-derived cell line MUTZ-3. Anti-interleukin (IL)-7 receptor antibodies (Abs) neutralized this effect indicating that TSLP binds to at least part of the IL-7 receptor complex. TSLP induced phosphorylation of signal transducer and activator of transcription (STAT)-5. In contrast to IL-7, TSLP-triggered STAT-5 phosphorylation was not preceded by activation of janus kinase (JAK) 3. These findings would be in accordance with the notion, raised previously for the mouse system, that TSLP leads to STAT-5 phosphorylation by activating other kinases than the JAKs. Some other signaling pathways stimulated by many cytokines are not involved in TSLP activity; thus, TSLP did not stimulate activation of ERK1,2 and p70S6K. Furthermore, neutralizing Abs raised against cytokines known to stimulate the growth of MUTZ-3 cells did not inhibit the proliferative effects of TSLP, suggesting that TSLP-induced growth was a direct effect. In summary, we describe the cloning of human TSLP and its proliferative effects on a myeloid cell line. TSLP-induced proliferation is preceded by phosphorylation of STAT-5, but not of JAK 3.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cloning, Molecular
  • Cytokines / analysis
  • Cytokines / genetics*
  • Cytokines / pharmacology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Milk Proteins*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • STAT5 Transcription Factor
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Thymic Stromal Lymphopoietin
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Milk Proteins
  • STAT5 Transcription Factor
  • Trans-Activators
  • Protein-Tyrosine Kinases
  • Thymic Stromal Lymphopoietin