Quantitative analysis of immune-mediated stimulation of tumor necrosis factor-alpha in macrophages measured at the level of mRNA and protein synthesis

Ann Hematol. 2001 Dec;80(12):733-6. doi: 10.1007/s00277-001-0383-x. Epub 2001 Oct 23.

Abstract

Expression of cytokines such as tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS) has been associated with inflammatory and regulatory immune reactions. Antigen-presenting cells, especially macrophages, play a central role in directing immune responses by synthesizing different cytokines. For the analysis of cytokine synthesis, we compared quantitative changes in mRNA and protein synthesis of TNF-alpha in RAW 264.7 cells stimulated with 0.1 ng/ml LPS. TNF-alpha mRNA was quantified using the LightCycler SYBR Green technology (Idaho Technology, Inc., Salt Lake City, Utah, USA). RAW 264.7 cells showed a basal TNF-alpha mRNA expression which increased approximately sixfold after 2 h of stimulation with LPS. TNF-alpha synthesis was analyzed at the protein level using a mouse-specific sandwich enzyme-linked immunosorbent assay (ELISA) and indicated a 56-fold increase in TNF-alpha protein concentration after 4 h. Thus, real-time polymerase chain reaction (PCR) is a sensitive and rapid method for quantitative determination of LPS-induced TNF-alpha expression. However, it requires extremely robust reaction parameters to be reliable for accurate quantification.

MeSH terms

  • Actins / genetics
  • Animals
  • Cell Line
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression
  • Kinetics
  • Lipopolysaccharides / pharmacology
  • Macrophages / chemistry
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Mice
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis*
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Actins
  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha