TGF-beta1 treated murine dendritic cells are maturation resistant and down-regulate Toll-like receptor 4 expression

J Zhejiang Univ Sci. 2004 Oct;5(10):1239-44. doi: 10.1631/jzus.2004.1239.

Abstract

Objective: To explore the effects of transforming growth factor beta1 (TGF-beta1) on dendritic cells (DC).

Methods: Murine bone marrow cells were cultured with GM-CSF and TGF-beta1 to develop TGF-beta1-treated DC (TGFbeta-DC). Then they were stimulated by lipopolysaccharide (LPS). Their phenotypes were assessed by flow cytometry (FCM). The allogeneic stimulating capacity of DC was measured by mixed lymphocyte reaction (MLR) using BrdU ELISA method and IL-12p70 protein was detected by ELISA. The expression of Toll-like receptor 4 (TLR4) was analyzed by semi quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and FCM.

Results: Compared to immature DC (imDC) cultured by GM-CSF alone, the TGFbeta-DC express lower CD80, CD86, I-Ab and CD40. The TGFbeta-DC were resistant to maturation with LPS. Maturation resistance was evident from a failure to up-regulate co-stimulatory molecules (CMs), to stimulate larger T cells proliferation and to enhance secretion of IL-12p70. We also found that TGF-beta1 could down-regulate TLR4 expression on TGFbeta-DC.

Conclusion: TGFbeta-DC are resistant to maturation stimulus (LPS) and might have some correlation with the down-modulation of TLR4 expression.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology*
  • Down-Regulation / drug effects
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Toll-Like Receptor 4
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1

Substances

  • Cytokines
  • Lipopolysaccharides
  • Receptors, Cell Surface
  • Tgfb1 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1