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Cyclic AMP stimulates platelet-derived growth factor B chain mRNA expression in murine macrophage cell lines

E J Kovacs1, S Vanstedum

  • 1Department of Cell Biology, Neurobiology, and Anatomy Loyola University Maywood IL 60153 USA.

Mediators of Inflammation
|January 1, 1995
PubMed

Insights

Activators of cyclic AMP (cAMP) differentially regulate cytokine gene expression in macrophages. While platelet-derived growth factor B chain mRNA is induced by cAMP, interleukin-1beta and tumor necrosis factor alpha require lipopolysaccharide (LPS) for induction.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Prostaglandin E2 (PGE2) is known to influence cytokine production by modulating intracellular cyclic adenosine monophosphate (cAMP) levels.
  • Understanding the precise mechanisms of cytokine regulation in immune cells is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the differential expression of cytokine genes in murine macrophages stimulated with various cAMP activators.
  • To elucidate the role of cAMP signaling pathways in the regulation of specific cytokine gene expression, including platelet-derived growth factor B chain (PDGF B), interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha).

Main Methods:

  • Murine macrophages were cultured and treated with cAMP activators (PGE2, dibutyryl cAMP, forskolin) with or without lipopolysaccharide (LPS).
  • Gene expression levels of IL-1beta, TNF-alpha, and PDGF B chain mRNA were analyzed using quantitative methods.

Main Results:

  • Macrophages expressed low levels of TNF-alpha and PDGF B chain mRNA, and no IL-1beta mRNA, prior to stimulation.
  • Treatment with cAMP inducers (PGE2, dibutyryl cAMP, forskolin) led to the induction of PDGF B chain mRNA.
  • Forskolin significantly induced PDGF B chain mRNA expression, comparable to LPS.
  • cAMP inducers enhanced IL-1beta and TNF-alpha mRNA expression only in the presence of LPS.
  • The combined effect of forskolin and LPS on PDGF B chain mRNA did not show synergy, suggesting LPS-mediated effects are not solely cAMP-dependent.

Conclusions:

  • Intracellular cAMP levels differentially regulate cytokine gene expression in macrophages.
  • PDGF B chain mRNA expression is induced by cAMP activators independently of LPS.
  • IL-1beta and TNF-alpha mRNA induction by cAMP activators is dependent on the presence of LPS.
  • These findings highlight the complex interplay between cAMP signaling and LPS-mediated pathways in macrophage cytokine production.

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