TGF-β1 prevents up-regulation of the P2X7 receptor by IFN-γ and LPS in leukemic THP-1 monocytes

Biochim Biophys Acta. 2010 Nov;1798(11):2058-66. doi: 10.1016/j.bbamem.2010.07.022. Epub 2010 Jul 27.


The P2X7 receptor is an extracellular ATP-gated cation channel critical in inflammation and immunity, and can be up-regulated by IFN-γ and LPS. This study aimed to examine the effect of TGF-β1 on the up-regulation of P2X7 function and expression in leukemic THP-1 monocytes differentiated with IFN-γ and LPS. Cell-surface molecules including P2X7 were examined by immunofluorescence staining. Total P2X7 protein and mRNA was assessed by immunoblotting and RT-PCR respectively. P2X7 function was evaluated by ATP-induced cation dye uptake measurements. Cell-surface P2X7 was present on THP-1 cells differentiated for 3days with IFN-γ and LPS but not on undifferentiated THP-1 cells. ATP induced ethidium(+) uptake into differentiated but not undifferentiated THP-1 cells, and the P2X7 antagonist, KN-62, impaired ATP-induced ethidium(+) uptake. Co-incubation of cells with TGF-β1 plus IFN-γ and LPS prevented the up-regulation of P2X7 expression and ATP-induced ethidium(+) uptake in a concentration-dependent fashion with a maximum effect at 5ng/ml and with an IC(50) of ~0.4ng/ml. Moreover, ATP-induced YO-PRO-1(2+) uptake and IL-1β release were abrogated in cells co-incubated with TGF-β1. TGF-β1 also abrogated the amount of total P2X7 protein and mRNA induced by IFN-γ and LPS. Finally, TGF-β1 prevented the up-regulation of cell-surface CD86, but not CD14 and MHC class II, by IFN-γ and LPS. These results indicate that TGF-β1 prevents the up-regulation of P2X7 function and expression by IFN-γ and LPS in THP-1 monocytes. This suggests that TGF-β1 may limit P2X7-mediated processes in inflammation and immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Adenosine Triphosphate / pharmacology
  • Antigens, CD / analysis
  • Apyrase / analysis
  • B7-2 Antigen / analysis
  • Cells, Cultured
  • Humans
  • Interferon-gamma / pharmacology*
  • Lipopolysaccharide Receptors / analysis
  • Lipopolysaccharides / pharmacology*
  • Monocytes / chemistry
  • Monocytes / drug effects*
  • Receptors, Purinergic P2 / analysis
  • Receptors, Purinergic P2 / drug effects*
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / physiology
  • Receptors, Purinergic P2X7
  • Transforming Growth Factor beta1 / pharmacology*
  • Up-Regulation


  • Antigens, CD
  • B7-2 Antigen
  • CD86 protein, human
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • P2RX7 protein, human
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Transforming Growth Factor beta1
  • KN 62
  • Interferon-gamma
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Adenosine Triphosphate
  • Apyrase
  • CD39 antigen