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Augmented expression of platelet-activating factor receptor gene by TNF-alpha through transcriptional activation in

P Dagenais1, M Thivierge, J L Parent

  • 1Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Canada.

Journal of Leukocyte Biology
|January 1, 1997
PubMed

Insights

Tumor necrosis factor alpha (TNF-alpha) up-regulates the platelet-activating factor receptor (PAFR) in human monocytes. This enhances monocyte inflammatory responses, providing new insights into inflammatory disease pathogenesis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Tumor necrosis factor alpha (TNF-alpha) is a key inflammatory cytokine.
  • Platelet-activating factor (PAF) and its receptor (PAFR) are involved in inflammatory and infectious diseases.
  • PAFR is constitutively expressed on monocytes, crucial immune cells.

Purpose of the Study:

  • To investigate the effect of TNF-alpha on PAFR expression in human monocytes.
  • To elucidate the molecular mechanisms underlying TNF-alpha's influence on PAFR.
  • To assess the functional consequences of TNF-alpha-induced PAFR modulation on monocyte responses.

Main Methods:

  • Human monocytes were stimulated with TNF-alpha.
  • PAFR mRNA expression was quantified using quantitative PCR.
  • Transcriptional regulation was assessed using Actinomycin D.
  • PAFR binding sites were measured using radioligand binding assays ([3H]WEB 2086).
  • Interleukin-6 (IL-6) production in response to PAF was measured.

Main Results:

  • TNF-alpha significantly increased PAFR mRNA expression in human monocytes.
  • The increase in PAFR mRNA was transcriptional and occurred within 1-24 hours.
  • TNF-alpha led to a 43% increase in specific PAFR binding sites without altering receptor affinity.
  • TNF-alpha-pretreated monocytes showed enhanced IL-6 production in response to PAF.

Conclusions:

  • TNF-alpha up-regulates PAFR expression at both the mRNA and protein levels in human monocytes.
  • This TNF-alpha-mediated increase in PAFR enhances monocyte responsiveness to PAF.
  • These findings reveal a novel interaction between TNF-alpha and PAF signaling pathways in monocytes, contributing to inflammatory processes.

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