Thrombospondin-1 differentially regulates release of IL-6 and IL-10 by human monocytic cell line U937

Biochem Biophys Res Commun. 2002 Feb 8;290(5):1551-7. doi: 10.1006/bbrc.2002.6386.


We investigated possible regulatory effects of thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein, on cytokine release from macrophages. Immobilized TSP-1 enhanced IL-6 release from the human monocytic U937 cells stimulated with phorbol myristate acetate and LPS, whereas it inhibited IL-10 release. The 70-kDa fragment of TSP-1 containing the type 1 repeats showed the same regulatory effects. The enhanced IL-6 release by TSP-1 was inhibited by anti-CD36 antibody or antibody against the sequence of the binding site to CD36 in the type 1 repeats of TSP-1. Conversely, the decrease in IL-10 release by TSP-1 was strengthened by the blocking of the interaction between CD36 and TSP-1. Furthermore, the involvement of TGF-beta1 in the inhibition of IL-10 release by TSP-1 was indicated by the facts that (i) TSP-1 induced activation of TGF-beta1 produced by the U937 cells, (ii) exogenously added TGF-beta1 inhibited IL-10 release, and (iii) antibody against TGF-beta1 blocked the inhibition of IL-10 release by TSP-1. Together, the present findings suggest that TSP-1 enhances IL-6 release from macrophages by interaction with CD36, whereas IL-10 release is regulated by the balance between the enhancing effect of TSP-1 via CD36 and the suppressive effect by TSP-1-activated TGF-beta1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / physiology
  • CD36 Antigens / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / metabolism*
  • Interleukin-6 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Protein Binding
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thrombospondin 1 / metabolism
  • Thrombospondin 1 / physiology*
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1
  • U937 Cells / drug effects
  • U937 Cells / metabolism*


  • Adjuvants, Immunologic
  • CD36 Antigens
  • Immunosuppressive Agents
  • Interleukin-6
  • Lipopolysaccharides
  • TGFB1 protein, human
  • Thrombospondin 1
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Interleukin-10
  • Tetradecanoylphorbol Acetate