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Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
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Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes

Published on: May 31, 2018

Pharmacological modulation of TNF production in macrophages

Hen-I Lin1, Shi-Jye Chu, David Wang

  • 1Department of Internal Medicine, Catholic Cardinal Tien Hospital, Fu-Jen Catholic University, Taipei Hsien, Taiwan, ROC. linlll@ms28.hinet.net

Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi
|April 3, 2004
PubMed

Insights

Five drugs were tested for their effects on tumor necrosis factor (TNF) production in macrophages. Pentoxyfilline, VZ 65, and AA-861 inhibited TNF production, with VZ 65 and AA-861 showing complex effects on TNF mRNA stability.

Area of Science:

  • Immunology
  • Pharmacology

Background:

  • Tumor necrosis factor (TNF) production is tightly regulated due to its potential for severe harm, such as in septic shock.
  • Prostaglandins and leukotrienes are implicated in modulating TNF production by monocytes and macrophages.

Purpose of the Study:

  • To investigate the effects of five drugs from three classes (cyclooxygenase inhibitors, 5-lipoxygenase inhibitors, and methylxanthines) on TNF production in RAW264 murine macrophages stimulated with lipopolysaccharide (LPS).

Main Methods:

  • RAW264 macrophages were stimulated with LPS.
  • The effects of indomethacin, ibuprofen, VZ 65, AA-861, and pentoxyfilline (PTX) on TNF production were assessed.
  • Prostaglandin E2 (PGE2), intracellular cAMP, and Leukotriene B4 (LTB4) levels were measured.
  • TNF mRNA transcription and stability were analyzed.

Main Results:

  • Indomethacin and ibuprofen increased TNF production.
  • PTX, VZ 65, and AA-861 significantly inhibited TNF production, regardless of administration timing relative to LPS.
  • VZ 65 and AA-861 inhibited PGE2 production and intracellular cAMP, and potentially act independently of LTB4.
  • All three inhibitors (PTX, VZ 65, AA-861) reduced TNF mRNA transcription, but VZ 65 and AA-861 enhanced mRNA stability.

Conclusions:

  • PTX reduces TNF protein by inhibiting mRNA transcription.
  • VZ 65 and AA-861 exhibit dual effects, inhibiting TNF transcription while enhancing mRNA stability, suggesting complex regulatory mechanisms.
  • These findings offer insights into novel therapeutic targets for controlling excessive TNF production.

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