Reciprocal regulation of LTA4 hydrolase expression in human monocytes by γ-interferon and interleukins 4 and 13: Potential relevance to leukotriene regulation in glomerular disease

Angel Montero, George M. Nassar, Susumu Uda, Karen A. Munger, Kamal F. Badr

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aims: Leukotriene A4 (LTA4) hydrolase catalyzes the final step in the synthesis of leukotriene B4 (LTB4). TH-1- and TH-2-derived cytokines may regulate LTB4 synthesis by monocytes through their actions on the expression of LTA4 hydrolase. Methods: Freshly isolated monocytes were incubated with pro- and anti-inflammatory cytokines for 36 h. mRNA expression was determined by Northern blot, protein expression was determined by Western blot and LTB4 synthesis was determined by ELISA. Results: Interferon-γ (a TH-2-derived cytokine) increased significantly LTA4 hydrolase mRNA expression, whereas interleukin (IL)-4 and IL-13 (both TH-2-derived cytokines) decreased LTA4 hydrolase mRNA expression in these cells. The same effects were seen on the expression of immunoreactive LTA4 hydrolase after incubating the monocytes with either TH-1- or TH-2-derived cytokines. The monocyte-derived cytokine IL-1β did not show any significant effect on LTA4 hydrolase mRNA expression. When LTB4 release was measured, both IL-1β and interferon-γ-significantly increased LTB4 production by monocytes, while TH-2 cytokines (IL-4 and IL-13) decreased it. Conclusion: The opposing effects of TH-1- and TH-2-derived cytokines on the expression of LTA4 hydrolase mRNA may regulate LTB4 synthesis by monocytes during inflammation. Copyright (C) 1999 S. Karger AG, Basel.

Original languageEnglish (US)
Pages (from-to)258-265
Number of pages8
JournalExperimental Nephrology
Volume8
Issue number4-5
StatePublished - Jul 2000
Externally publishedYes

Keywords

  • γ-Interferon
  • Cytokines
  • Interleukins
  • Leukotrienes
  • LTA hydrolase

ASJC Scopus subject areas

  • Nephrology

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