IFN-gamma and lipopolysaccharide differentially modulate expression of tumor necrosis factor receptor mRNA in murine

C S Tannenbaum1, J A Major, T A Hamilton

  • 1Department of Immunology, Cleveland Clinic Foundation, OH 44195.

Insights

Lipopolysaccharide (LPS) increases tumor necrosis factor receptor (TNFR) mRNA, but interferon-gamma (IFN-gamma) suppresses this LPS-induced enhancement. These immune signaling molecules modulate TNFR expression through transcriptional control, impacting TNF-alpha

Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Tumor necrosis factor receptor (TNFR) plays a crucial role in immune responses.
  • Understanding the regulation of TNFR expression is vital for controlling inflammatory processes.

Purpose of the Study:

  • To investigate the effects of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) on TNF receptor (TNFR) mRNA expression in murine peritoneal macrophages.
  • To elucidate the mechanisms underlying the modulation of TNFR expression by these immune mediators.

Main Methods:

  • Murine peritoneal macrophages were stimulated with LPS and/or IFN-gamma.
  • Messenger RNA (mRNA) expression for type I and type II TNFR was analyzed using hybridization with cDNA probes.
  • The role of protein synthesis was assessed by including cycloheximide in treatment protocols.

Main Results:

  • LPS significantly enhanced the expression of type II TNFR mRNA in a time-dependent manner.
  • IFN-gamma abrogated the LPS-induced enhancement of type II TNFR mRNA expression in a dose-dependent and sequence-dependent manner.
  • Type I TNFR mRNA levels remained largely unaffected by LPS and IFN-gamma treatments.
  • Modulation of type II TNFR expression by LPS and IFN-gamma occurred at the transcriptional level and was independent of protein synthesis.

Conclusions:

  • IFN-gamma exerts a suppressive effect on LPS-induced type II TNFR expression, contrasting with its synergistic role in TNF-alpha production.
  • LPS and IFN-gamma differentially regulate TNFR subtypes, suggesting complex crosstalk in immune signaling pathways.
  • These findings highlight intricate mechanisms by which LPS and IFN-gamma modulate TNF-alpha's physiological actions via transcriptional control of its receptors.